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Periprosthetic Joint Infections Not Increased by RA Biologics
LONDON – Patients with rheumatoid arthritis who have had total joint replacement are not at greater risk of joint infection if they use biologic agents when compared with conventional disease-modifying drugs.
New data from the German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) show that the overall rate of periprosthetic joint infection is low, at 1%, and remains low regardless of the treatment type.
"A lot of patients with RA have to undergo joint replacement," said Dr. Anja Strangfeld of the German Rheumatism Research Center Berlin, where the biologics register is based.
During an interview, Dr. Strangfeld noted that concern has been voiced about the use of anti-tumor necrosis factor (TNF) agents in patients who need a joint replacement because of the possibility of an increased risk of serious infections.
"It was also thought that in people who already have prostheses, a joint infection will be more likely to occur after starting biologic treatment, especially with anti-TNF agents," Dr. Strangfeld observed.
"The hypothesis was that microorganisms could enter the joint during the surgery [and] form a protective biofilm," but this biofilm might get disrupted when anti-TNF treatment is started, she said. This disruption allows the infective agent to spread and cause infection.
However, of 1,495 total joint replacements in 1,013 patients, very few got infected.
"In our whole register, we only found 15 periprosthetic joint infections, and this means that 1% of the procedures got infected. That’s good news, as it seems that there is not an increased risk for patients," Dr. Strangfeld said.
Until May 2010, 7,536 patients with RA were included in the RABBIT database and were treated with conventional disease-modifying antirheumatic drugs (DMARDs), anti-TNFs, or other biologic agents (tocilizumab, rituximab, abatacept).
Only total replacements of the hip, knee, shoulder, or ankle were included in the analysis, and patients had received joint prostheses both before and after enrollment. The mean exposure to biologic therapy before joint surgery was 2.7 years.
There was no significant difference between the percentage of joints that became infected in patients treated with DMARDs versus those treated with anti-TNF agents (1.5% vs. 1.5%; P = .077)
There was also no significant difference observed among individual anti-TNF drugs, with rates of 1.5%, 1.4%, and 0.9% for adalimumab, etanercept, and infliximab, respectively.
These incidence rates are in line with data from Danish and Finnish arthroplasty registries, in which infection rates of 0.7% and 1.3% have been reported.
In patients treated with tocilizumab, rituximab, or abatacept, no periprosthetic infections occurred, although the number of patient-years of observation were much lower than that for anti-TNFs and DMARDS.
The microorganism responsible for the joint infection was reported in only 10 cases – with Staphylococcus spp. being the most common culprit (6 cases).
When asked whether patients who underwent joint replacement surgery might have to take antibiotic prophylaxis, Dr. Strangfeld noted that this was something that the current analysis could not determine but would be interesting to look at.
These findings suggest that patients who need to have a joint replacement and who are already being treated with a biologic agent should have no great cause to worry about contracting an infection.
"For patients who already have a joint replacement, they also don’t have to worry that much if they start a biologic agent," Dr. Strangfeld said.
RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
LONDON – Patients with rheumatoid arthritis who have had total joint replacement are not at greater risk of joint infection if they use biologic agents when compared with conventional disease-modifying drugs.
New data from the German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) show that the overall rate of periprosthetic joint infection is low, at 1%, and remains low regardless of the treatment type.
"A lot of patients with RA have to undergo joint replacement," said Dr. Anja Strangfeld of the German Rheumatism Research Center Berlin, where the biologics register is based.
During an interview, Dr. Strangfeld noted that concern has been voiced about the use of anti-tumor necrosis factor (TNF) agents in patients who need a joint replacement because of the possibility of an increased risk of serious infections.
"It was also thought that in people who already have prostheses, a joint infection will be more likely to occur after starting biologic treatment, especially with anti-TNF agents," Dr. Strangfeld observed.
"The hypothesis was that microorganisms could enter the joint during the surgery [and] form a protective biofilm," but this biofilm might get disrupted when anti-TNF treatment is started, she said. This disruption allows the infective agent to spread and cause infection.
However, of 1,495 total joint replacements in 1,013 patients, very few got infected.
"In our whole register, we only found 15 periprosthetic joint infections, and this means that 1% of the procedures got infected. That’s good news, as it seems that there is not an increased risk for patients," Dr. Strangfeld said.
Until May 2010, 7,536 patients with RA were included in the RABBIT database and were treated with conventional disease-modifying antirheumatic drugs (DMARDs), anti-TNFs, or other biologic agents (tocilizumab, rituximab, abatacept).
Only total replacements of the hip, knee, shoulder, or ankle were included in the analysis, and patients had received joint prostheses both before and after enrollment. The mean exposure to biologic therapy before joint surgery was 2.7 years.
There was no significant difference between the percentage of joints that became infected in patients treated with DMARDs versus those treated with anti-TNF agents (1.5% vs. 1.5%; P = .077)
There was also no significant difference observed among individual anti-TNF drugs, with rates of 1.5%, 1.4%, and 0.9% for adalimumab, etanercept, and infliximab, respectively.
These incidence rates are in line with data from Danish and Finnish arthroplasty registries, in which infection rates of 0.7% and 1.3% have been reported.
In patients treated with tocilizumab, rituximab, or abatacept, no periprosthetic infections occurred, although the number of patient-years of observation were much lower than that for anti-TNFs and DMARDS.
The microorganism responsible for the joint infection was reported in only 10 cases – with Staphylococcus spp. being the most common culprit (6 cases).
When asked whether patients who underwent joint replacement surgery might have to take antibiotic prophylaxis, Dr. Strangfeld noted that this was something that the current analysis could not determine but would be interesting to look at.
These findings suggest that patients who need to have a joint replacement and who are already being treated with a biologic agent should have no great cause to worry about contracting an infection.
"For patients who already have a joint replacement, they also don’t have to worry that much if they start a biologic agent," Dr. Strangfeld said.
RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
LONDON – Patients with rheumatoid arthritis who have had total joint replacement are not at greater risk of joint infection if they use biologic agents when compared with conventional disease-modifying drugs.
New data from the German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) show that the overall rate of periprosthetic joint infection is low, at 1%, and remains low regardless of the treatment type.
"A lot of patients with RA have to undergo joint replacement," said Dr. Anja Strangfeld of the German Rheumatism Research Center Berlin, where the biologics register is based.
During an interview, Dr. Strangfeld noted that concern has been voiced about the use of anti-tumor necrosis factor (TNF) agents in patients who need a joint replacement because of the possibility of an increased risk of serious infections.
"It was also thought that in people who already have prostheses, a joint infection will be more likely to occur after starting biologic treatment, especially with anti-TNF agents," Dr. Strangfeld observed.
"The hypothesis was that microorganisms could enter the joint during the surgery [and] form a protective biofilm," but this biofilm might get disrupted when anti-TNF treatment is started, she said. This disruption allows the infective agent to spread and cause infection.
However, of 1,495 total joint replacements in 1,013 patients, very few got infected.
"In our whole register, we only found 15 periprosthetic joint infections, and this means that 1% of the procedures got infected. That’s good news, as it seems that there is not an increased risk for patients," Dr. Strangfeld said.
Until May 2010, 7,536 patients with RA were included in the RABBIT database and were treated with conventional disease-modifying antirheumatic drugs (DMARDs), anti-TNFs, or other biologic agents (tocilizumab, rituximab, abatacept).
Only total replacements of the hip, knee, shoulder, or ankle were included in the analysis, and patients had received joint prostheses both before and after enrollment. The mean exposure to biologic therapy before joint surgery was 2.7 years.
There was no significant difference between the percentage of joints that became infected in patients treated with DMARDs versus those treated with anti-TNF agents (1.5% vs. 1.5%; P = .077)
There was also no significant difference observed among individual anti-TNF drugs, with rates of 1.5%, 1.4%, and 0.9% for adalimumab, etanercept, and infliximab, respectively.
These incidence rates are in line with data from Danish and Finnish arthroplasty registries, in which infection rates of 0.7% and 1.3% have been reported.
In patients treated with tocilizumab, rituximab, or abatacept, no periprosthetic infections occurred, although the number of patient-years of observation were much lower than that for anti-TNFs and DMARDS.
The microorganism responsible for the joint infection was reported in only 10 cases – with Staphylococcus spp. being the most common culprit (6 cases).
When asked whether patients who underwent joint replacement surgery might have to take antibiotic prophylaxis, Dr. Strangfeld noted that this was something that the current analysis could not determine but would be interesting to look at.
These findings suggest that patients who need to have a joint replacement and who are already being treated with a biologic agent should have no great cause to worry about contracting an infection.
"For patients who already have a joint replacement, they also don’t have to worry that much if they start a biologic agent," Dr. Strangfeld said.
RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
FROM THE ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY
Major Finding: Fifteen joint infections occurred in 1,495 patients, with 1% of conventional DMARD-treated and 1.5% of anti-TNF–treated patients experiencing joint infection (P less than .77).
Data Source: Data analysis of 7,536 RA patients enrolled in the German biologics register RABBIT until May 2010.
Disclosures: RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
Periprosthetic Joint Infections Not Increased by RA Biologics
LONDON – Patients with rheumatoid arthritis who have had total joint replacement are not at greater risk of joint infection if they use biologic agents when compared with conventional disease-modifying drugs.
New data from the German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) show that the overall rate of periprosthetic joint infection is low, at 1%, and remains low regardless of the treatment type.
"A lot of patients with RA have to undergo joint replacement," said Dr. Anja Strangfeld of the German Rheumatism Research Center Berlin, where the biologics register is based.
During an interview, Dr. Strangfeld noted that concern has been voiced about the use of anti-tumor necrosis factor (TNF) agents in patients who need a joint replacement because of the possibility of an increased risk of serious infections.
"It was also thought that in people who already have prostheses, a joint infection will be more likely to occur after starting biologic treatment, especially with anti-TNF agents," Dr. Strangfeld observed.
"The hypothesis was that microorganisms could enter the joint during the surgery [and] form a protective biofilm," but this biofilm might get disrupted when anti-TNF treatment is started, she said. This disruption allows the infective agent to spread and cause infection.
However, of 1,495 total joint replacements in 1,013 patients, very few got infected.
"In our whole register, we only found 15 periprosthetic joint infections, and this means that 1% of the procedures got infected. That’s good news, as it seems that there is not an increased risk for patients," Dr. Strangfeld said.
Until May 2010, 7,536 patients with RA were included in the RABBIT database and were treated with conventional disease-modifying antirheumatic drugs (DMARDs), anti-TNFs, or other biologic agents (tocilizumab, rituximab, abatacept).
Only total replacements of the hip, knee, shoulder, or ankle were included in the analysis, and patients had received joint prostheses both before and after enrollment. The mean exposure to biologic therapy before joint surgery was 2.7 years.
There was no significant difference between the percentage of joints that became infected in patients treated with DMARDs versus those treated with anti-TNF agents (1.5% vs. 1.5%; P = .077)
There was also no significant difference observed among individual anti-TNF drugs, with rates of 1.5%, 1.4%, and 0.9% for adalimumab, etanercept, and infliximab, respectively.
These incidence rates are in line with data from Danish and Finnish arthroplasty registries, in which infection rates of 0.7% and 1.3% have been reported.
In patients treated with tocilizumab, rituximab, or abatacept, no periprosthetic infections occurred, although the number of patient-years of observation were much lower than that for anti-TNFs and DMARDS.
The microorganism responsible for the joint infection was reported in only 10 cases – with Staphylococcus spp. being the most common culprit (6 cases).
When asked whether patients who underwent joint replacement surgery might have to take antibiotic prophylaxis, Dr. Strangfeld noted that this was something that the current analysis could not determine but would be interesting to look at.
These findings suggest that patients who need to have a joint replacement and who are already being treated with a biologic agent should have no great cause to worry about contracting an infection.
"For patients who already have a joint replacement, they also don’t have to worry that much if they start a biologic agent," Dr. Strangfeld said.
RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
LONDON – Patients with rheumatoid arthritis who have had total joint replacement are not at greater risk of joint infection if they use biologic agents when compared with conventional disease-modifying drugs.
New data from the German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) show that the overall rate of periprosthetic joint infection is low, at 1%, and remains low regardless of the treatment type.
"A lot of patients with RA have to undergo joint replacement," said Dr. Anja Strangfeld of the German Rheumatism Research Center Berlin, where the biologics register is based.
During an interview, Dr. Strangfeld noted that concern has been voiced about the use of anti-tumor necrosis factor (TNF) agents in patients who need a joint replacement because of the possibility of an increased risk of serious infections.
"It was also thought that in people who already have prostheses, a joint infection will be more likely to occur after starting biologic treatment, especially with anti-TNF agents," Dr. Strangfeld observed.
"The hypothesis was that microorganisms could enter the joint during the surgery [and] form a protective biofilm," but this biofilm might get disrupted when anti-TNF treatment is started, she said. This disruption allows the infective agent to spread and cause infection.
However, of 1,495 total joint replacements in 1,013 patients, very few got infected.
"In our whole register, we only found 15 periprosthetic joint infections, and this means that 1% of the procedures got infected. That’s good news, as it seems that there is not an increased risk for patients," Dr. Strangfeld said.
Until May 2010, 7,536 patients with RA were included in the RABBIT database and were treated with conventional disease-modifying antirheumatic drugs (DMARDs), anti-TNFs, or other biologic agents (tocilizumab, rituximab, abatacept).
Only total replacements of the hip, knee, shoulder, or ankle were included in the analysis, and patients had received joint prostheses both before and after enrollment. The mean exposure to biologic therapy before joint surgery was 2.7 years.
There was no significant difference between the percentage of joints that became infected in patients treated with DMARDs versus those treated with anti-TNF agents (1.5% vs. 1.5%; P = .077)
There was also no significant difference observed among individual anti-TNF drugs, with rates of 1.5%, 1.4%, and 0.9% for adalimumab, etanercept, and infliximab, respectively.
These incidence rates are in line with data from Danish and Finnish arthroplasty registries, in which infection rates of 0.7% and 1.3% have been reported.
In patients treated with tocilizumab, rituximab, or abatacept, no periprosthetic infections occurred, although the number of patient-years of observation were much lower than that for anti-TNFs and DMARDS.
The microorganism responsible for the joint infection was reported in only 10 cases – with Staphylococcus spp. being the most common culprit (6 cases).
When asked whether patients who underwent joint replacement surgery might have to take antibiotic prophylaxis, Dr. Strangfeld noted that this was something that the current analysis could not determine but would be interesting to look at.
These findings suggest that patients who need to have a joint replacement and who are already being treated with a biologic agent should have no great cause to worry about contracting an infection.
"For patients who already have a joint replacement, they also don’t have to worry that much if they start a biologic agent," Dr. Strangfeld said.
RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
LONDON – Patients with rheumatoid arthritis who have had total joint replacement are not at greater risk of joint infection if they use biologic agents when compared with conventional disease-modifying drugs.
New data from the German biologics register RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) show that the overall rate of periprosthetic joint infection is low, at 1%, and remains low regardless of the treatment type.
"A lot of patients with RA have to undergo joint replacement," said Dr. Anja Strangfeld of the German Rheumatism Research Center Berlin, where the biologics register is based.
During an interview, Dr. Strangfeld noted that concern has been voiced about the use of anti-tumor necrosis factor (TNF) agents in patients who need a joint replacement because of the possibility of an increased risk of serious infections.
"It was also thought that in people who already have prostheses, a joint infection will be more likely to occur after starting biologic treatment, especially with anti-TNF agents," Dr. Strangfeld observed.
"The hypothesis was that microorganisms could enter the joint during the surgery [and] form a protective biofilm," but this biofilm might get disrupted when anti-TNF treatment is started, she said. This disruption allows the infective agent to spread and cause infection.
However, of 1,495 total joint replacements in 1,013 patients, very few got infected.
"In our whole register, we only found 15 periprosthetic joint infections, and this means that 1% of the procedures got infected. That’s good news, as it seems that there is not an increased risk for patients," Dr. Strangfeld said.
Until May 2010, 7,536 patients with RA were included in the RABBIT database and were treated with conventional disease-modifying antirheumatic drugs (DMARDs), anti-TNFs, or other biologic agents (tocilizumab, rituximab, abatacept).
Only total replacements of the hip, knee, shoulder, or ankle were included in the analysis, and patients had received joint prostheses both before and after enrollment. The mean exposure to biologic therapy before joint surgery was 2.7 years.
There was no significant difference between the percentage of joints that became infected in patients treated with DMARDs versus those treated with anti-TNF agents (1.5% vs. 1.5%; P = .077)
There was also no significant difference observed among individual anti-TNF drugs, with rates of 1.5%, 1.4%, and 0.9% for adalimumab, etanercept, and infliximab, respectively.
These incidence rates are in line with data from Danish and Finnish arthroplasty registries, in which infection rates of 0.7% and 1.3% have been reported.
In patients treated with tocilizumab, rituximab, or abatacept, no periprosthetic infections occurred, although the number of patient-years of observation were much lower than that for anti-TNFs and DMARDS.
The microorganism responsible for the joint infection was reported in only 10 cases – with Staphylococcus spp. being the most common culprit (6 cases).
When asked whether patients who underwent joint replacement surgery might have to take antibiotic prophylaxis, Dr. Strangfeld noted that this was something that the current analysis could not determine but would be interesting to look at.
These findings suggest that patients who need to have a joint replacement and who are already being treated with a biologic agent should have no great cause to worry about contracting an infection.
"For patients who already have a joint replacement, they also don’t have to worry that much if they start a biologic agent," Dr. Strangfeld said.
RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
FROM THE ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY
Major Finding: Fifteen joint infections occurred in 1,495 patients, with 1% of conventional DMARD-treated and 1.5% of anti-TNF–treated patients experiencing joint infection (P less than .77).
Data Source: Data analysis of 7,536 RA patients enrolled in the German biologics register RABBIT until May 2010.
Disclosures: RABBIT is supported by a joint, unconditional grant from the following German manufacturers of biologic agents: Abbott, Amgen/Swedish Orphan Biovitrum, Bristol-Myers Squibb, Essex/MSD, Pfizer, Roche, and UCB. Dr. Strangfeld had no personal financial disclosures.
Brentuximab Benefits Hodgkin's Patients Ineligible for Transplant
LONDON – The investigational agent brentuximab vedotin appears to have a beneficial effect in patients with refractory or relapsed Hodgkin’s lymphoma who are ineligible for or have refused to have an autologous stem cell transplant.
A retrospective analysis of two phase I studies performed with the drug used as a single agent have shown that almost one-third of these heavily pretreated patients are able to achieve an objective response to treatment.
Indeed, 6 of 20 patients (30%) aged a median of 32 years achieved an objective response (two complete and four partial remissions). The response can last longer than 6 months, with one patient achieving a durable remission for more than 2 years that later allowed for transplantation.
"These are very encouraging results in patients with [an] unmet need, and additional studies are ongoing," Dr. Ranjana Advani of Stanford University Medical Center in Palo Alto, Calif., said at the annual congress of the European Hematology Association.
"Patients who have primary refractory disease or fail to achieve a remission at relapse have a dismal outcome," Dr. Advani observed. She added that long-term survival prospects for such patients "were pretty bleak, with median overall survival in a small series as low as 4 months."
Brentuximab vedotin is a novel antibody-drug conjugate that comprises an anti-CD30 monoclonal antibody and a synthetic antimicrotubule agent, monomethyl auristatin E (MMAE). After binding to CD30 on the surface of T and B cells, the antibody-drug conjugate is internalized, the link between antibody and drug is severed, and MMAE is released – thus targeting malignant cells while, in theory, leaving normal cells unscathed.
MMAE is a potent antimicrotubule agent, and as with the taxanes, one of the expected side effects of the drug could be peripheral neuropathy. Although this was not seen in the small number of patients discussed by Dr. Advani, she said that peripheral neuropathy, mostly sensory, had been observed in about 15% of patients treated in the clinical trials program to date.
"Adverse events were seen in over 25% of patients, and these were not necessarily drug related; they could have been even disease related," Dr. Advani reported. Common side effects included fatigue (45%); nausea (40%); pyrexia (35%); decreased weight and diarrhea (30% each); vomiting, back pain, decreased appetite, anemia, and night sweats (25% each).
There were no deaths within 30 days of receiving the last dose of the novel agent.
The current findings add to data released separately from a pivotal phase II trial, recently updated and presented at this year’s American Society of Clinical Oncology meeting in Chicago. In that trial (J. Clin. Oncol. 2011 29[suppl.]: abstract 8031), brentuximab vedotin (SGN-35) induced objective responses in 75% of patients with relapsed or refractory Hodgkin’s disease; 34% achieved a durable complete remission, with two-thirds of patients remaining in complete remission.
Brentuximab has also recently been linked to durable remissions in patients with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL), an aggressive subtype of peripheral T-cell lymphoma.
The Food and Drug Administration has granted brentuximab vedotin orphan drug status for the treatment of Hodgkin’s lymphoma and sALCL.
Further studies are underway, and include the phase III AETHERA trial – which is comparing brentuximab vedotin to placebo in high-risk patients with Hodgkin’s lymphoma after autologous stem cell transplantation. Another phase I trial is also looking at the combination of brentuximab vedotin and the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen as de novo treatment in Hodgkin’s lymphoma.
Seattle Genetics and Millennium: the Takeda Oncology Co. funded the research. Dr. Advani disclosed acting as a principal investigator and receiving research support and advisory board fees from the company.
LONDON – The investigational agent brentuximab vedotin appears to have a beneficial effect in patients with refractory or relapsed Hodgkin’s lymphoma who are ineligible for or have refused to have an autologous stem cell transplant.
A retrospective analysis of two phase I studies performed with the drug used as a single agent have shown that almost one-third of these heavily pretreated patients are able to achieve an objective response to treatment.
Indeed, 6 of 20 patients (30%) aged a median of 32 years achieved an objective response (two complete and four partial remissions). The response can last longer than 6 months, with one patient achieving a durable remission for more than 2 years that later allowed for transplantation.
"These are very encouraging results in patients with [an] unmet need, and additional studies are ongoing," Dr. Ranjana Advani of Stanford University Medical Center in Palo Alto, Calif., said at the annual congress of the European Hematology Association.
"Patients who have primary refractory disease or fail to achieve a remission at relapse have a dismal outcome," Dr. Advani observed. She added that long-term survival prospects for such patients "were pretty bleak, with median overall survival in a small series as low as 4 months."
Brentuximab vedotin is a novel antibody-drug conjugate that comprises an anti-CD30 monoclonal antibody and a synthetic antimicrotubule agent, monomethyl auristatin E (MMAE). After binding to CD30 on the surface of T and B cells, the antibody-drug conjugate is internalized, the link between antibody and drug is severed, and MMAE is released – thus targeting malignant cells while, in theory, leaving normal cells unscathed.
MMAE is a potent antimicrotubule agent, and as with the taxanes, one of the expected side effects of the drug could be peripheral neuropathy. Although this was not seen in the small number of patients discussed by Dr. Advani, she said that peripheral neuropathy, mostly sensory, had been observed in about 15% of patients treated in the clinical trials program to date.
"Adverse events were seen in over 25% of patients, and these were not necessarily drug related; they could have been even disease related," Dr. Advani reported. Common side effects included fatigue (45%); nausea (40%); pyrexia (35%); decreased weight and diarrhea (30% each); vomiting, back pain, decreased appetite, anemia, and night sweats (25% each).
There were no deaths within 30 days of receiving the last dose of the novel agent.
The current findings add to data released separately from a pivotal phase II trial, recently updated and presented at this year’s American Society of Clinical Oncology meeting in Chicago. In that trial (J. Clin. Oncol. 2011 29[suppl.]: abstract 8031), brentuximab vedotin (SGN-35) induced objective responses in 75% of patients with relapsed or refractory Hodgkin’s disease; 34% achieved a durable complete remission, with two-thirds of patients remaining in complete remission.
Brentuximab has also recently been linked to durable remissions in patients with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL), an aggressive subtype of peripheral T-cell lymphoma.
The Food and Drug Administration has granted brentuximab vedotin orphan drug status for the treatment of Hodgkin’s lymphoma and sALCL.
Further studies are underway, and include the phase III AETHERA trial – which is comparing brentuximab vedotin to placebo in high-risk patients with Hodgkin’s lymphoma after autologous stem cell transplantation. Another phase I trial is also looking at the combination of brentuximab vedotin and the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen as de novo treatment in Hodgkin’s lymphoma.
Seattle Genetics and Millennium: the Takeda Oncology Co. funded the research. Dr. Advani disclosed acting as a principal investigator and receiving research support and advisory board fees from the company.
LONDON – The investigational agent brentuximab vedotin appears to have a beneficial effect in patients with refractory or relapsed Hodgkin’s lymphoma who are ineligible for or have refused to have an autologous stem cell transplant.
A retrospective analysis of two phase I studies performed with the drug used as a single agent have shown that almost one-third of these heavily pretreated patients are able to achieve an objective response to treatment.
Indeed, 6 of 20 patients (30%) aged a median of 32 years achieved an objective response (two complete and four partial remissions). The response can last longer than 6 months, with one patient achieving a durable remission for more than 2 years that later allowed for transplantation.
"These are very encouraging results in patients with [an] unmet need, and additional studies are ongoing," Dr. Ranjana Advani of Stanford University Medical Center in Palo Alto, Calif., said at the annual congress of the European Hematology Association.
"Patients who have primary refractory disease or fail to achieve a remission at relapse have a dismal outcome," Dr. Advani observed. She added that long-term survival prospects for such patients "were pretty bleak, with median overall survival in a small series as low as 4 months."
Brentuximab vedotin is a novel antibody-drug conjugate that comprises an anti-CD30 monoclonal antibody and a synthetic antimicrotubule agent, monomethyl auristatin E (MMAE). After binding to CD30 on the surface of T and B cells, the antibody-drug conjugate is internalized, the link between antibody and drug is severed, and MMAE is released – thus targeting malignant cells while, in theory, leaving normal cells unscathed.
MMAE is a potent antimicrotubule agent, and as with the taxanes, one of the expected side effects of the drug could be peripheral neuropathy. Although this was not seen in the small number of patients discussed by Dr. Advani, she said that peripheral neuropathy, mostly sensory, had been observed in about 15% of patients treated in the clinical trials program to date.
"Adverse events were seen in over 25% of patients, and these were not necessarily drug related; they could have been even disease related," Dr. Advani reported. Common side effects included fatigue (45%); nausea (40%); pyrexia (35%); decreased weight and diarrhea (30% each); vomiting, back pain, decreased appetite, anemia, and night sweats (25% each).
There were no deaths within 30 days of receiving the last dose of the novel agent.
The current findings add to data released separately from a pivotal phase II trial, recently updated and presented at this year’s American Society of Clinical Oncology meeting in Chicago. In that trial (J. Clin. Oncol. 2011 29[suppl.]: abstract 8031), brentuximab vedotin (SGN-35) induced objective responses in 75% of patients with relapsed or refractory Hodgkin’s disease; 34% achieved a durable complete remission, with two-thirds of patients remaining in complete remission.
Brentuximab has also recently been linked to durable remissions in patients with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL), an aggressive subtype of peripheral T-cell lymphoma.
The Food and Drug Administration has granted brentuximab vedotin orphan drug status for the treatment of Hodgkin’s lymphoma and sALCL.
Further studies are underway, and include the phase III AETHERA trial – which is comparing brentuximab vedotin to placebo in high-risk patients with Hodgkin’s lymphoma after autologous stem cell transplantation. Another phase I trial is also looking at the combination of brentuximab vedotin and the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen as de novo treatment in Hodgkin’s lymphoma.
Seattle Genetics and Millennium: the Takeda Oncology Co. funded the research. Dr. Advani disclosed acting as a principal investigator and receiving research support and advisory board fees from the company.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
Major Finding: Six patients (30%) achieved an objective response (two complete and four partial remissions).
Data Source: Retrospective analysis of two phase I studies of brentuximab vedotin in 20 patients with relapsed or refractory Hodgkin’s lymphoma who were ineligible for or refused autologous stem cell transplantation.
Disclosures: Seattle Genetics and Millennium: the Takeda Oncology Co. funded the research. Dr. Advani disclosed acting as a principal investigator and receiving research support and advisory board fees from the company.
Rheumatoid Arthritis Patients Have High Expectations for Biologics
LONDON – Patients with rheumatoid arthritis have high expectations of how effective biologic therapies will be in comparison to standard disease-modifying antirheumatic drugs, according to the results of a survey conducted in Japan.
RA patients taking biologics experience higher levels of anxiety than do patients taking DMARDs (66% vs. 53%) over switching treatments, and greater disappointment (37% vs. 28%) when therapies fail to live up to their expectations, according to Keiko Funahashi, a pharmacist from the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, Kato City, Japan. She reported the results at the annual European Congress of Rheumatology.
RA treatment "has improved dramatically in the past 10 years. Due to the advent of biological products, patients’ treatment goals have also changed significantly," she added.
Indeed, the survey findings suggest that patients taking biologic agents are more likely to expect their treatment to eradicate joint pain and swelling rather than to just simply reduce it.
Ms. Funahashi and coauthor Dr. Tsukasa Matsubara, also of the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, performed the outpatient survey in order to understand what patients expected of their treatment, and to determine the influence of biologic or nonbiologic DMARDs on patient attitudes.
The anonymous survey consisted of a short set of simple questions asking about the type of past and current treatment received, whether medications had been switched, what patients needed to know before starting a new treatment, their expectations of such treatment, and if they were satisfied with the results. Patients were also asked to state what their goals for treatment were.
A total of 165 patients attending the Matsubara Mayflower Hospital as outpatients during a 1-month period in October 2010 participated in the survey. In all, 110 patients were receiving treatment with DMARDs, and 55 were receiving biologics. Most patients were aged 50-70 years, and had a disease duration of 10-20 years.
While there was no significant difference between the DMARD and biologic treatment groups in terms of their current methotrexate use (70.7% vs. 63.6%, respectively), patients treated with biologic agents were less likely to be treated with steroids (40.8% vs. 21.8%, P less than .05) or nonsteroidal anti-inflammatory drugs (39.1% vs. 9.1%, P less than .01).
Before starting a new treatment, around 70% of patients in each group responded that they wanted to know about the side effects and efficacy first. Patients about to take biologics also wanted to know about the monthly cost, which they had to pay themselves, Ms. Funahashi said in an interview.
"Before treatment, patients taking biologics understood their disease better and had higher goals than those patients treated with DMARDs," Ms. Funahashi said. In particular, biologic-treated patients expected to see greater prevention of joint destruction, improved quality of life, and greater reductions in joint pain and swelling.
While patient goals hardly changed before and after treatment with DMARDs, the biologics group switched from not just wanting to reduce joint pain and swelling to wishing to eradicate them altogether.
The main cause of disappointment with treatment for patients treated with DMARDs was side effects, while a lack of efficacy was at the root of most patients’ dissatisfaction with biologic treatment.
"The results suggest that patients treated with biologics expect higher efficacy," Ms. Funahashi observed. This could be due to the perception that the higher cost equates with better efficacy. The cost of treatment is an important issue in Japan and a consideration when the rheumatologist and patient consider options.
The survey findings also highlight the need for good patient education and communication, and the development of realistic treatment goals.
"Doctors and health professionals really have a duty, I think, to give people the appropriate information, as well as do a lot of signposting to patient organizations and groups that can offer peer support," said Ms. Kate Llewelyn, who is head of information services at the U.K. charity Arthritis Care, in an interview.
"Learning to self-manage and realize that you can take control of your arthritis and rheumatism is one of the key things to feeling like you’re actually tackling the disease rather than being a passive recipient of treatment," Ms. Llewelyn suggested.
Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
LONDON – Patients with rheumatoid arthritis have high expectations of how effective biologic therapies will be in comparison to standard disease-modifying antirheumatic drugs, according to the results of a survey conducted in Japan.
RA patients taking biologics experience higher levels of anxiety than do patients taking DMARDs (66% vs. 53%) over switching treatments, and greater disappointment (37% vs. 28%) when therapies fail to live up to their expectations, according to Keiko Funahashi, a pharmacist from the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, Kato City, Japan. She reported the results at the annual European Congress of Rheumatology.
RA treatment "has improved dramatically in the past 10 years. Due to the advent of biological products, patients’ treatment goals have also changed significantly," she added.
Indeed, the survey findings suggest that patients taking biologic agents are more likely to expect their treatment to eradicate joint pain and swelling rather than to just simply reduce it.
Ms. Funahashi and coauthor Dr. Tsukasa Matsubara, also of the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, performed the outpatient survey in order to understand what patients expected of their treatment, and to determine the influence of biologic or nonbiologic DMARDs on patient attitudes.
The anonymous survey consisted of a short set of simple questions asking about the type of past and current treatment received, whether medications had been switched, what patients needed to know before starting a new treatment, their expectations of such treatment, and if they were satisfied with the results. Patients were also asked to state what their goals for treatment were.
A total of 165 patients attending the Matsubara Mayflower Hospital as outpatients during a 1-month period in October 2010 participated in the survey. In all, 110 patients were receiving treatment with DMARDs, and 55 were receiving biologics. Most patients were aged 50-70 years, and had a disease duration of 10-20 years.
While there was no significant difference between the DMARD and biologic treatment groups in terms of their current methotrexate use (70.7% vs. 63.6%, respectively), patients treated with biologic agents were less likely to be treated with steroids (40.8% vs. 21.8%, P less than .05) or nonsteroidal anti-inflammatory drugs (39.1% vs. 9.1%, P less than .01).
Before starting a new treatment, around 70% of patients in each group responded that they wanted to know about the side effects and efficacy first. Patients about to take biologics also wanted to know about the monthly cost, which they had to pay themselves, Ms. Funahashi said in an interview.
"Before treatment, patients taking biologics understood their disease better and had higher goals than those patients treated with DMARDs," Ms. Funahashi said. In particular, biologic-treated patients expected to see greater prevention of joint destruction, improved quality of life, and greater reductions in joint pain and swelling.
While patient goals hardly changed before and after treatment with DMARDs, the biologics group switched from not just wanting to reduce joint pain and swelling to wishing to eradicate them altogether.
The main cause of disappointment with treatment for patients treated with DMARDs was side effects, while a lack of efficacy was at the root of most patients’ dissatisfaction with biologic treatment.
"The results suggest that patients treated with biologics expect higher efficacy," Ms. Funahashi observed. This could be due to the perception that the higher cost equates with better efficacy. The cost of treatment is an important issue in Japan and a consideration when the rheumatologist and patient consider options.
The survey findings also highlight the need for good patient education and communication, and the development of realistic treatment goals.
"Doctors and health professionals really have a duty, I think, to give people the appropriate information, as well as do a lot of signposting to patient organizations and groups that can offer peer support," said Ms. Kate Llewelyn, who is head of information services at the U.K. charity Arthritis Care, in an interview.
"Learning to self-manage and realize that you can take control of your arthritis and rheumatism is one of the key things to feeling like you’re actually tackling the disease rather than being a passive recipient of treatment," Ms. Llewelyn suggested.
Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
LONDON – Patients with rheumatoid arthritis have high expectations of how effective biologic therapies will be in comparison to standard disease-modifying antirheumatic drugs, according to the results of a survey conducted in Japan.
RA patients taking biologics experience higher levels of anxiety than do patients taking DMARDs (66% vs. 53%) over switching treatments, and greater disappointment (37% vs. 28%) when therapies fail to live up to their expectations, according to Keiko Funahashi, a pharmacist from the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, Kato City, Japan. She reported the results at the annual European Congress of Rheumatology.
RA treatment "has improved dramatically in the past 10 years. Due to the advent of biological products, patients’ treatment goals have also changed significantly," she added.
Indeed, the survey findings suggest that patients taking biologic agents are more likely to expect their treatment to eradicate joint pain and swelling rather than to just simply reduce it.
Ms. Funahashi and coauthor Dr. Tsukasa Matsubara, also of the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, performed the outpatient survey in order to understand what patients expected of their treatment, and to determine the influence of biologic or nonbiologic DMARDs on patient attitudes.
The anonymous survey consisted of a short set of simple questions asking about the type of past and current treatment received, whether medications had been switched, what patients needed to know before starting a new treatment, their expectations of such treatment, and if they were satisfied with the results. Patients were also asked to state what their goals for treatment were.
A total of 165 patients attending the Matsubara Mayflower Hospital as outpatients during a 1-month period in October 2010 participated in the survey. In all, 110 patients were receiving treatment with DMARDs, and 55 were receiving biologics. Most patients were aged 50-70 years, and had a disease duration of 10-20 years.
While there was no significant difference between the DMARD and biologic treatment groups in terms of their current methotrexate use (70.7% vs. 63.6%, respectively), patients treated with biologic agents were less likely to be treated with steroids (40.8% vs. 21.8%, P less than .05) or nonsteroidal anti-inflammatory drugs (39.1% vs. 9.1%, P less than .01).
Before starting a new treatment, around 70% of patients in each group responded that they wanted to know about the side effects and efficacy first. Patients about to take biologics also wanted to know about the monthly cost, which they had to pay themselves, Ms. Funahashi said in an interview.
"Before treatment, patients taking biologics understood their disease better and had higher goals than those patients treated with DMARDs," Ms. Funahashi said. In particular, biologic-treated patients expected to see greater prevention of joint destruction, improved quality of life, and greater reductions in joint pain and swelling.
While patient goals hardly changed before and after treatment with DMARDs, the biologics group switched from not just wanting to reduce joint pain and swelling to wishing to eradicate them altogether.
The main cause of disappointment with treatment for patients treated with DMARDs was side effects, while a lack of efficacy was at the root of most patients’ dissatisfaction with biologic treatment.
"The results suggest that patients treated with biologics expect higher efficacy," Ms. Funahashi observed. This could be due to the perception that the higher cost equates with better efficacy. The cost of treatment is an important issue in Japan and a consideration when the rheumatologist and patient consider options.
The survey findings also highlight the need for good patient education and communication, and the development of realistic treatment goals.
"Doctors and health professionals really have a duty, I think, to give people the appropriate information, as well as do a lot of signposting to patient organizations and groups that can offer peer support," said Ms. Kate Llewelyn, who is head of information services at the U.K. charity Arthritis Care, in an interview.
"Learning to self-manage and realize that you can take control of your arthritis and rheumatism is one of the key things to feeling like you’re actually tackling the disease rather than being a passive recipient of treatment," Ms. Llewelyn suggested.
Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
FROM THE ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY
Major Finding: Patients treated with biologics experienced higher levels of anxiety than did DMARD-treated patients (66% vs. 53%) over switching treatment, and expressed greater disappointment (37% vs. 28%) when therapies failed.
Data Source: Anonymous survey of 165 Japanese outpatients with RA; 110 were treated with DMARDs and 55 with biologic agents.
Disclosures: Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
Rheumatoid Arthritis Patients Have High Expectations for Biologics
LONDON – Patients with rheumatoid arthritis have high expectations of how effective biologic therapies will be in comparison to standard disease-modifying antirheumatic drugs, according to the results of a survey conducted in Japan.
RA patients taking biologics experience higher levels of anxiety than do patients taking DMARDs (66% vs. 53%) over switching treatments, and greater disappointment (37% vs. 28%) when therapies fail to live up to their expectations, according to Keiko Funahashi, a pharmacist from the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, Kato City, Japan. She reported the results at the annual European Congress of Rheumatology.
RA treatment "has improved dramatically in the past 10 years. Due to the advent of biological products, patients’ treatment goals have also changed significantly," she added.
Indeed, the survey findings suggest that patients taking biologic agents are more likely to expect their treatment to eradicate joint pain and swelling rather than to just simply reduce it.
Ms. Funahashi and coauthor Dr. Tsukasa Matsubara, also of the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, performed the outpatient survey in order to understand what patients expected of their treatment, and to determine the influence of biologic or nonbiologic DMARDs on patient attitudes.
The anonymous survey consisted of a short set of simple questions asking about the type of past and current treatment received, whether medications had been switched, what patients needed to know before starting a new treatment, their expectations of such treatment, and if they were satisfied with the results. Patients were also asked to state what their goals for treatment were.
A total of 165 patients attending the Matsubara Mayflower Hospital as outpatients during a 1-month period in October 2010 participated in the survey. In all, 110 patients were receiving treatment with DMARDs, and 55 were receiving biologics. Most patients were aged 50-70 years, and had a disease duration of 10-20 years.
While there was no significant difference between the DMARD and biologic treatment groups in terms of their current methotrexate use (70.7% vs. 63.6%, respectively), patients treated with biologic agents were less likely to be treated with steroids (40.8% vs. 21.8%, P less than .05) or nonsteroidal anti-inflammatory drugs (39.1% vs. 9.1%, P less than .01).
Before starting a new treatment, around 70% of patients in each group responded that they wanted to know about the side effects and efficacy first. Patients about to take biologics also wanted to know about the monthly cost, which they had to pay themselves, Ms. Funahashi said in an interview.
"Before treatment, patients taking biologics understood their disease better and had higher goals than those patients treated with DMARDs," Ms. Funahashi said. In particular, biologic-treated patients expected to see greater prevention of joint destruction, improved quality of life, and greater reductions in joint pain and swelling.
While patient goals hardly changed before and after treatment with DMARDs, the biologics group switched from not just wanting to reduce joint pain and swelling to wishing to eradicate them altogether.
The main cause of disappointment with treatment for patients treated with DMARDs was side effects, while a lack of efficacy was at the root of most patients’ dissatisfaction with biologic treatment.
"The results suggest that patients treated with biologics expect higher efficacy," Ms. Funahashi observed. This could be due to the perception that the higher cost equates with better efficacy. The cost of treatment is an important issue in Japan and a consideration when the rheumatologist and patient consider options.
The survey findings also highlight the need for good patient education and communication, and the development of realistic treatment goals.
"Doctors and health professionals really have a duty, I think, to give people the appropriate information, as well as do a lot of signposting to patient organizations and groups that can offer peer support," said Ms. Kate Llewelyn, who is head of information services at the U.K. charity Arthritis Care, in an interview.
"Learning to self-manage and realize that you can take control of your arthritis and rheumatism is one of the key things to feeling like you’re actually tackling the disease rather than being a passive recipient of treatment," Ms. Llewelyn suggested.
Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
LONDON – Patients with rheumatoid arthritis have high expectations of how effective biologic therapies will be in comparison to standard disease-modifying antirheumatic drugs, according to the results of a survey conducted in Japan.
RA patients taking biologics experience higher levels of anxiety than do patients taking DMARDs (66% vs. 53%) over switching treatments, and greater disappointment (37% vs. 28%) when therapies fail to live up to their expectations, according to Keiko Funahashi, a pharmacist from the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, Kato City, Japan. She reported the results at the annual European Congress of Rheumatology.
RA treatment "has improved dramatically in the past 10 years. Due to the advent of biological products, patients’ treatment goals have also changed significantly," she added.
Indeed, the survey findings suggest that patients taking biologic agents are more likely to expect their treatment to eradicate joint pain and swelling rather than to just simply reduce it.
Ms. Funahashi and coauthor Dr. Tsukasa Matsubara, also of the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, performed the outpatient survey in order to understand what patients expected of their treatment, and to determine the influence of biologic or nonbiologic DMARDs on patient attitudes.
The anonymous survey consisted of a short set of simple questions asking about the type of past and current treatment received, whether medications had been switched, what patients needed to know before starting a new treatment, their expectations of such treatment, and if they were satisfied with the results. Patients were also asked to state what their goals for treatment were.
A total of 165 patients attending the Matsubara Mayflower Hospital as outpatients during a 1-month period in October 2010 participated in the survey. In all, 110 patients were receiving treatment with DMARDs, and 55 were receiving biologics. Most patients were aged 50-70 years, and had a disease duration of 10-20 years.
While there was no significant difference between the DMARD and biologic treatment groups in terms of their current methotrexate use (70.7% vs. 63.6%, respectively), patients treated with biologic agents were less likely to be treated with steroids (40.8% vs. 21.8%, P less than .05) or nonsteroidal anti-inflammatory drugs (39.1% vs. 9.1%, P less than .01).
Before starting a new treatment, around 70% of patients in each group responded that they wanted to know about the side effects and efficacy first. Patients about to take biologics also wanted to know about the monthly cost, which they had to pay themselves, Ms. Funahashi said in an interview.
"Before treatment, patients taking biologics understood their disease better and had higher goals than those patients treated with DMARDs," Ms. Funahashi said. In particular, biologic-treated patients expected to see greater prevention of joint destruction, improved quality of life, and greater reductions in joint pain and swelling.
While patient goals hardly changed before and after treatment with DMARDs, the biologics group switched from not just wanting to reduce joint pain and swelling to wishing to eradicate them altogether.
The main cause of disappointment with treatment for patients treated with DMARDs was side effects, while a lack of efficacy was at the root of most patients’ dissatisfaction with biologic treatment.
"The results suggest that patients treated with biologics expect higher efficacy," Ms. Funahashi observed. This could be due to the perception that the higher cost equates with better efficacy. The cost of treatment is an important issue in Japan and a consideration when the rheumatologist and patient consider options.
The survey findings also highlight the need for good patient education and communication, and the development of realistic treatment goals.
"Doctors and health professionals really have a duty, I think, to give people the appropriate information, as well as do a lot of signposting to patient organizations and groups that can offer peer support," said Ms. Kate Llewelyn, who is head of information services at the U.K. charity Arthritis Care, in an interview.
"Learning to self-manage and realize that you can take control of your arthritis and rheumatism is one of the key things to feeling like you’re actually tackling the disease rather than being a passive recipient of treatment," Ms. Llewelyn suggested.
Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
LONDON – Patients with rheumatoid arthritis have high expectations of how effective biologic therapies will be in comparison to standard disease-modifying antirheumatic drugs, according to the results of a survey conducted in Japan.
RA patients taking biologics experience higher levels of anxiety than do patients taking DMARDs (66% vs. 53%) over switching treatments, and greater disappointment (37% vs. 28%) when therapies fail to live up to their expectations, according to Keiko Funahashi, a pharmacist from the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, Kato City, Japan. She reported the results at the annual European Congress of Rheumatology.
RA treatment "has improved dramatically in the past 10 years. Due to the advent of biological products, patients’ treatment goals have also changed significantly," she added.
Indeed, the survey findings suggest that patients taking biologic agents are more likely to expect their treatment to eradicate joint pain and swelling rather than to just simply reduce it.
Ms. Funahashi and coauthor Dr. Tsukasa Matsubara, also of the Matsubara Mayflower Hospital and Research Institute of Joint Diseases, performed the outpatient survey in order to understand what patients expected of their treatment, and to determine the influence of biologic or nonbiologic DMARDs on patient attitudes.
The anonymous survey consisted of a short set of simple questions asking about the type of past and current treatment received, whether medications had been switched, what patients needed to know before starting a new treatment, their expectations of such treatment, and if they were satisfied with the results. Patients were also asked to state what their goals for treatment were.
A total of 165 patients attending the Matsubara Mayflower Hospital as outpatients during a 1-month period in October 2010 participated in the survey. In all, 110 patients were receiving treatment with DMARDs, and 55 were receiving biologics. Most patients were aged 50-70 years, and had a disease duration of 10-20 years.
While there was no significant difference between the DMARD and biologic treatment groups in terms of their current methotrexate use (70.7% vs. 63.6%, respectively), patients treated with biologic agents were less likely to be treated with steroids (40.8% vs. 21.8%, P less than .05) or nonsteroidal anti-inflammatory drugs (39.1% vs. 9.1%, P less than .01).
Before starting a new treatment, around 70% of patients in each group responded that they wanted to know about the side effects and efficacy first. Patients about to take biologics also wanted to know about the monthly cost, which they had to pay themselves, Ms. Funahashi said in an interview.
"Before treatment, patients taking biologics understood their disease better and had higher goals than those patients treated with DMARDs," Ms. Funahashi said. In particular, biologic-treated patients expected to see greater prevention of joint destruction, improved quality of life, and greater reductions in joint pain and swelling.
While patient goals hardly changed before and after treatment with DMARDs, the biologics group switched from not just wanting to reduce joint pain and swelling to wishing to eradicate them altogether.
The main cause of disappointment with treatment for patients treated with DMARDs was side effects, while a lack of efficacy was at the root of most patients’ dissatisfaction with biologic treatment.
"The results suggest that patients treated with biologics expect higher efficacy," Ms. Funahashi observed. This could be due to the perception that the higher cost equates with better efficacy. The cost of treatment is an important issue in Japan and a consideration when the rheumatologist and patient consider options.
The survey findings also highlight the need for good patient education and communication, and the development of realistic treatment goals.
"Doctors and health professionals really have a duty, I think, to give people the appropriate information, as well as do a lot of signposting to patient organizations and groups that can offer peer support," said Ms. Kate Llewelyn, who is head of information services at the U.K. charity Arthritis Care, in an interview.
"Learning to self-manage and realize that you can take control of your arthritis and rheumatism is one of the key things to feeling like you’re actually tackling the disease rather than being a passive recipient of treatment," Ms. Llewelyn suggested.
Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
FROM THE ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY
Major Finding: Patients treated with biologics experienced higher levels of anxiety than did DMARD-treated patients (66% vs. 53%) over switching treatment, and expressed greater disappointment (37% vs. 28%) when therapies failed.
Data Source: Anonymous survey of 165 Japanese outpatients with RA; 110 were treated with DMARDs and 55 with biologic agents.
Disclosures: Ms. Funahashi, her coauthor Dr. Matsubara, and Ms. Llewelyn had no conflicts of interest to declare.
Treat HIV-Related Hodgkin's Like Non-HIV Disease
LONDON – HIV-infected patients with Hodgkin’s lymphoma can be treated more or less the same as any other Hodgkin’s patient, according to new data from the German HIV-related Lymphoma Study Group.
In a prospective, multicenter study of 108 patients with Hodgkin’s lymphoma (HL), all of whom were HIV positive, a risk-adapted treatment strategy was found to be feasible while patients were being treated with HAART (highly active antiretroviral therapy).
"I think the main message is that the prognosis [of patients with HIV-related HL] has dramatically improved with the [use of] HAART and with the stage- and risk-adapted treatment approach," study investigator Dr. Marcus Hentrich said in a June 11 interview at the annual congress of the European Hematology Association, where he presented the study.
"The results are approaching those we have obtained in the HIV-negative population," added Dr. Hentrich of Harlaching Hospital Munich. The findings show that "not every patient needs to be treated with full intensity" for six to eight courses of chemotherapy; rather, "we can distinguish [treatment] depending on the Hodgkin’s stage."
HL is one of the most common non–AIDS-defining cancers that often presents at an advanced stage. To date, there have been few prospective studies looking at how best to treat patients who are both HIV positive and have the hematologic malignancy; indeed, patients with HIV-related HL are often excluded from HL clinical trials. As a consequence, how best to manage such patients remains unknown (Adv. Hematol. 2011 [doi:10.1155/2011/402682]).
Combination therapy regimens have largely been used to treat HL in HIV-infected patients because of the generally late presentation of the disease, and controlling HIV infection via HAART has also been shown to improve the outcome of HL (Ann. Oncol. 2006;17:914-9).
The current study presented by Dr. Hentrich was conducted between March 2004 and October 2010. It included 100 male and 8 female patients with HL who were HIV positive, and its aim was to see whether a risk-adapted treatment strategy that was used in HIV-negative patients with HL could be applied to those infected with HIV.
Treatment for HL was determined by the stage of disease, with two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) used with involved-field radiotherapy (30 Gy) in early-stage patients (that is, those with stage I-II HL and no additional risk factors).
In intermediate-stage patients (that is, those with stage I-II disease plus additional risk factors, such as large mediastinal tumor, extranodal involvement, and three or more lymph node regions involved), treatment consisted of four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus the same radiotherapy regimen.
More advanced HL (stage III-IV) was treated with six to eight cycles of BEACOPP plus facultative radiotherapy (30 Gy initial bulk or rest).
In patients with very advanced HIV infection and a poor performance status, the BEACOPP regimen could be replaced by ABVD, and the dose of ABVD reduced according to individual circumstances.
The median age of recruited patients was 43.9 years (range, 27-70 years). The majority (65%) had advanced disease, with 14% identified as having intermediate-stage HL, and 21% with early-stage disease. Extranodal involvement was observed in about half of patients (54%), and almost two-thirds (65%) had B-symptoms (which includes systemic symptoms such as fever, night sweats, and weight loss; B-symptoms can occur in both HL and non-HL).
Most (77%) patients had received HAART, and the median time from HIV to HL diagnosis was 5.9 years (range, 0-26 years).
After 26 months’ follow-up, 96%, 100%, and 84% of patients with early-, intermediate-, and advanced-stage HL, respectively, were in complete remission.
Perhaps not surprisingly, some advanced-stage patients fared worse, with four (6%) toxic and one (1.4%) unknown cause of death, five (7%) cases of early progression, and one (1.4%) partial remission in this group. One (4%) patient in the early-stage group also died because of toxicity.
Dr. Hentrich pointed out that treatment relapses and failures mainly occurred in patients with advanced disease.
Grade 3/4 toxicity was common and tended to occur in more patients who were treated with BEACOPP than AVBD, but the differences were statistically significantly only in the early-stage patients. The major hematologic toxicity was severe neutropenia.
At 2-years, progression-free and overall survival were 91.7% and 90.2%, respectively, for the whole population, and did not differ greatly between early-, intermediate-, and advanced-stage disease. However, patients with advanced disease and advanced HIV infection were more likely to have a reduced overall survival, compared with the other two groups of patients.
"The next strategy is to focus the amount of intensity to special patients, so we want to incorporate early PET scans after two cycles [of chemotherapy] and then de-escalate therapy or even escalate therapy," Dr. Hentrich said.
Dr. Hentrich had no financial disclosures or conflicts of interest.
LONDON – HIV-infected patients with Hodgkin’s lymphoma can be treated more or less the same as any other Hodgkin’s patient, according to new data from the German HIV-related Lymphoma Study Group.
In a prospective, multicenter study of 108 patients with Hodgkin’s lymphoma (HL), all of whom were HIV positive, a risk-adapted treatment strategy was found to be feasible while patients were being treated with HAART (highly active antiretroviral therapy).
"I think the main message is that the prognosis [of patients with HIV-related HL] has dramatically improved with the [use of] HAART and with the stage- and risk-adapted treatment approach," study investigator Dr. Marcus Hentrich said in a June 11 interview at the annual congress of the European Hematology Association, where he presented the study.
"The results are approaching those we have obtained in the HIV-negative population," added Dr. Hentrich of Harlaching Hospital Munich. The findings show that "not every patient needs to be treated with full intensity" for six to eight courses of chemotherapy; rather, "we can distinguish [treatment] depending on the Hodgkin’s stage."
HL is one of the most common non–AIDS-defining cancers that often presents at an advanced stage. To date, there have been few prospective studies looking at how best to treat patients who are both HIV positive and have the hematologic malignancy; indeed, patients with HIV-related HL are often excluded from HL clinical trials. As a consequence, how best to manage such patients remains unknown (Adv. Hematol. 2011 [doi:10.1155/2011/402682]).
Combination therapy regimens have largely been used to treat HL in HIV-infected patients because of the generally late presentation of the disease, and controlling HIV infection via HAART has also been shown to improve the outcome of HL (Ann. Oncol. 2006;17:914-9).
The current study presented by Dr. Hentrich was conducted between March 2004 and October 2010. It included 100 male and 8 female patients with HL who were HIV positive, and its aim was to see whether a risk-adapted treatment strategy that was used in HIV-negative patients with HL could be applied to those infected with HIV.
Treatment for HL was determined by the stage of disease, with two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) used with involved-field radiotherapy (30 Gy) in early-stage patients (that is, those with stage I-II HL and no additional risk factors).
In intermediate-stage patients (that is, those with stage I-II disease plus additional risk factors, such as large mediastinal tumor, extranodal involvement, and three or more lymph node regions involved), treatment consisted of four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus the same radiotherapy regimen.
More advanced HL (stage III-IV) was treated with six to eight cycles of BEACOPP plus facultative radiotherapy (30 Gy initial bulk or rest).
In patients with very advanced HIV infection and a poor performance status, the BEACOPP regimen could be replaced by ABVD, and the dose of ABVD reduced according to individual circumstances.
The median age of recruited patients was 43.9 years (range, 27-70 years). The majority (65%) had advanced disease, with 14% identified as having intermediate-stage HL, and 21% with early-stage disease. Extranodal involvement was observed in about half of patients (54%), and almost two-thirds (65%) had B-symptoms (which includes systemic symptoms such as fever, night sweats, and weight loss; B-symptoms can occur in both HL and non-HL).
Most (77%) patients had received HAART, and the median time from HIV to HL diagnosis was 5.9 years (range, 0-26 years).
After 26 months’ follow-up, 96%, 100%, and 84% of patients with early-, intermediate-, and advanced-stage HL, respectively, were in complete remission.
Perhaps not surprisingly, some advanced-stage patients fared worse, with four (6%) toxic and one (1.4%) unknown cause of death, five (7%) cases of early progression, and one (1.4%) partial remission in this group. One (4%) patient in the early-stage group also died because of toxicity.
Dr. Hentrich pointed out that treatment relapses and failures mainly occurred in patients with advanced disease.
Grade 3/4 toxicity was common and tended to occur in more patients who were treated with BEACOPP than AVBD, but the differences were statistically significantly only in the early-stage patients. The major hematologic toxicity was severe neutropenia.
At 2-years, progression-free and overall survival were 91.7% and 90.2%, respectively, for the whole population, and did not differ greatly between early-, intermediate-, and advanced-stage disease. However, patients with advanced disease and advanced HIV infection were more likely to have a reduced overall survival, compared with the other two groups of patients.
"The next strategy is to focus the amount of intensity to special patients, so we want to incorporate early PET scans after two cycles [of chemotherapy] and then de-escalate therapy or even escalate therapy," Dr. Hentrich said.
Dr. Hentrich had no financial disclosures or conflicts of interest.
LONDON – HIV-infected patients with Hodgkin’s lymphoma can be treated more or less the same as any other Hodgkin’s patient, according to new data from the German HIV-related Lymphoma Study Group.
In a prospective, multicenter study of 108 patients with Hodgkin’s lymphoma (HL), all of whom were HIV positive, a risk-adapted treatment strategy was found to be feasible while patients were being treated with HAART (highly active antiretroviral therapy).
"I think the main message is that the prognosis [of patients with HIV-related HL] has dramatically improved with the [use of] HAART and with the stage- and risk-adapted treatment approach," study investigator Dr. Marcus Hentrich said in a June 11 interview at the annual congress of the European Hematology Association, where he presented the study.
"The results are approaching those we have obtained in the HIV-negative population," added Dr. Hentrich of Harlaching Hospital Munich. The findings show that "not every patient needs to be treated with full intensity" for six to eight courses of chemotherapy; rather, "we can distinguish [treatment] depending on the Hodgkin’s stage."
HL is one of the most common non–AIDS-defining cancers that often presents at an advanced stage. To date, there have been few prospective studies looking at how best to treat patients who are both HIV positive and have the hematologic malignancy; indeed, patients with HIV-related HL are often excluded from HL clinical trials. As a consequence, how best to manage such patients remains unknown (Adv. Hematol. 2011 [doi:10.1155/2011/402682]).
Combination therapy regimens have largely been used to treat HL in HIV-infected patients because of the generally late presentation of the disease, and controlling HIV infection via HAART has also been shown to improve the outcome of HL (Ann. Oncol. 2006;17:914-9).
The current study presented by Dr. Hentrich was conducted between March 2004 and October 2010. It included 100 male and 8 female patients with HL who were HIV positive, and its aim was to see whether a risk-adapted treatment strategy that was used in HIV-negative patients with HL could be applied to those infected with HIV.
Treatment for HL was determined by the stage of disease, with two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) used with involved-field radiotherapy (30 Gy) in early-stage patients (that is, those with stage I-II HL and no additional risk factors).
In intermediate-stage patients (that is, those with stage I-II disease plus additional risk factors, such as large mediastinal tumor, extranodal involvement, and three or more lymph node regions involved), treatment consisted of four cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) plus the same radiotherapy regimen.
More advanced HL (stage III-IV) was treated with six to eight cycles of BEACOPP plus facultative radiotherapy (30 Gy initial bulk or rest).
In patients with very advanced HIV infection and a poor performance status, the BEACOPP regimen could be replaced by ABVD, and the dose of ABVD reduced according to individual circumstances.
The median age of recruited patients was 43.9 years (range, 27-70 years). The majority (65%) had advanced disease, with 14% identified as having intermediate-stage HL, and 21% with early-stage disease. Extranodal involvement was observed in about half of patients (54%), and almost two-thirds (65%) had B-symptoms (which includes systemic symptoms such as fever, night sweats, and weight loss; B-symptoms can occur in both HL and non-HL).
Most (77%) patients had received HAART, and the median time from HIV to HL diagnosis was 5.9 years (range, 0-26 years).
After 26 months’ follow-up, 96%, 100%, and 84% of patients with early-, intermediate-, and advanced-stage HL, respectively, were in complete remission.
Perhaps not surprisingly, some advanced-stage patients fared worse, with four (6%) toxic and one (1.4%) unknown cause of death, five (7%) cases of early progression, and one (1.4%) partial remission in this group. One (4%) patient in the early-stage group also died because of toxicity.
Dr. Hentrich pointed out that treatment relapses and failures mainly occurred in patients with advanced disease.
Grade 3/4 toxicity was common and tended to occur in more patients who were treated with BEACOPP than AVBD, but the differences were statistically significantly only in the early-stage patients. The major hematologic toxicity was severe neutropenia.
At 2-years, progression-free and overall survival were 91.7% and 90.2%, respectively, for the whole population, and did not differ greatly between early-, intermediate-, and advanced-stage disease. However, patients with advanced disease and advanced HIV infection were more likely to have a reduced overall survival, compared with the other two groups of patients.
"The next strategy is to focus the amount of intensity to special patients, so we want to incorporate early PET scans after two cycles [of chemotherapy] and then de-escalate therapy or even escalate therapy," Dr. Hentrich said.
Dr. Hentrich had no financial disclosures or conflicts of interest.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
Major Finding: At 2-years, progression-free and overall survival rates were 91.7% and 90.2%, respectively, for the whole population.
Data Source: Prospective, multicenter study of 108 HIV-associated Hodgkin’s lymphoma patients who were treated with chemotherapy according to the stage of hematologic malignancy.
Disclosures: Dr. Hentrich had no financial disclosures or conflicts of interest.
Stopping Dasatinib and Nilotinib Explored in Chronic Myeloid Leukemia
LONDON – Stopping treatment with dasatinib and nilotinib might be safe in chronic myeloid leukemia patients who have achieved sustained and complete molecular responses, early data from a pilot study have shown.
The STOP 2GTKI study is a successor to the STop IMatinib (STIM) trial, which showed that stopping treatment with imatinib – the first-generation tyrosine kinase inhibitor (TKI) of BCR-ABL – could be feasible in patients who achieve long-lasting complete molecular responses (Lancet Oncol.2010;11:1029-35).
Although still preliminary, the new data suggest that it could be possible to do the same with these second-generation TKIs in patients who were previously intolerant or resistant to treatment with imatinib, Dr. Delphine Réa said at the annual Congress of the European Hematology Association.
"There are different kinds of reasons why we should aim at stopping tyrosine kinase inhibitors in chronic myeloid leukemia patients," said Dr. Réa of Hôpital Saint-Louis in Paris.
"The first one relates to patients. From the patients’ perspective it’s very important to have the hope of feeling cured," said Dr. Réa, a member of the French team that performed both the STIM and the STOP 2G-TKI studies.
Other reasons given include avoiding the adverse effects of prolonged therapy on quality of life, and reducing health care costs by steering clear of unnecessary long-term treatment for what becomes a chronic disease. It’s also important for clinicians to be able to show that a treatment really does cure a disease, she said, and the only way to do that is to stop the treatment.
Dr. Réa presented early data on 14 patients who had been enrolled in the STOP 2G-TKI pilot study until May 2011 and for whom there was at least 6 months’ follow-up. The median age of patients was 59 years.
"I think it’s very important to have 6 months’ follow-up at least because in the STop IMatinib trial, most of the relapses occurred within the first 6 months," Dr. Réa explained in an interview after her presentation.
"Here we didn’t have any relapses after 6 months," Dr. Réa added. "For the nine patients who didn’t relapse, the median follow-up is 10 months." The duration of time that these patients remained treatment free was between 6 months and 19 months.
For inclusion in the study, patients had to be aged 18 years or older with chronic or acute phase chronic myeloid leukemia at diagnosis, and be receiving ongoing dasatinib or nilotinib treatment after intolerance or resistance to imatinib therapy. TKI treatment had to have been administered for at least 3 years, and patients needed to have undetectable levels of BCR-ABL with at least 20,000 copies of ABL.
The primary end point was the achievement of a stable major molecular response (MMR) at 6 months, determined by monthly blood counts and real-time quantitative polymerase chain reaction for the first year of discontinuation, then every 2-3 months thereafter. Bone marrow smears and cytogenic and mutational analysis are undertaken if there is a rise in BCR-ABL above an internationally standardized (IS) ratio of 1%. Patients are re-treated with dasatinib or nilotinib if there is a loss of MMR of more than 0.1% IS.
Results showed that at 6 months’ follow-up, 71% of patients had a persistent MMR, and 64% remained treatment free. Five patients restarted TKI treatment at a median of 5 months, and four patients lost MMR after a median of 3 months. However, the patients who lost major molecular response retained their sensitivity to TKIs, and BCR-ABL was undetectable in all five patients who restarted therapy.
Asked what these results could mean for clinical practice, Dr. Réa noted that they are an early indicator that stopping treatment with second-generation TKIs will probably be an option for some patients who achieve good responses. Careful (at least monthly) follow-up of patients who cease treatment would be required, at least in the research setting.
"We don’t know, but we hope the relapse rate will be lower than we have seen with imatinib [discontinuation]," Dr. Réa said. She added, however, that there is an indication that the relapse rate could actually be higher than that seen in the STIM trial.
As yet, the optimal duration of treatment with a second-generation TKI before discontinuation can be attempted is unknown. "In the STop IMatinib trial, it seems to be between 4 and 5 years," Dr. Réa observed. "So I don’t think it will be reasonable to stop treatment before that period of time."
Further results from the trial can be expected later in the year, Dr. Réa noted. To date, 23 patients have been recruited and 8 more are to be included in the trial.
Dr. Réa disclosed serving on advisory boards of Bristol-Myers Squibb and Novartis.
LONDON – Stopping treatment with dasatinib and nilotinib might be safe in chronic myeloid leukemia patients who have achieved sustained and complete molecular responses, early data from a pilot study have shown.
The STOP 2GTKI study is a successor to the STop IMatinib (STIM) trial, which showed that stopping treatment with imatinib – the first-generation tyrosine kinase inhibitor (TKI) of BCR-ABL – could be feasible in patients who achieve long-lasting complete molecular responses (Lancet Oncol.2010;11:1029-35).
Although still preliminary, the new data suggest that it could be possible to do the same with these second-generation TKIs in patients who were previously intolerant or resistant to treatment with imatinib, Dr. Delphine Réa said at the annual Congress of the European Hematology Association.
"There are different kinds of reasons why we should aim at stopping tyrosine kinase inhibitors in chronic myeloid leukemia patients," said Dr. Réa of Hôpital Saint-Louis in Paris.
"The first one relates to patients. From the patients’ perspective it’s very important to have the hope of feeling cured," said Dr. Réa, a member of the French team that performed both the STIM and the STOP 2G-TKI studies.
Other reasons given include avoiding the adverse effects of prolonged therapy on quality of life, and reducing health care costs by steering clear of unnecessary long-term treatment for what becomes a chronic disease. It’s also important for clinicians to be able to show that a treatment really does cure a disease, she said, and the only way to do that is to stop the treatment.
Dr. Réa presented early data on 14 patients who had been enrolled in the STOP 2G-TKI pilot study until May 2011 and for whom there was at least 6 months’ follow-up. The median age of patients was 59 years.
"I think it’s very important to have 6 months’ follow-up at least because in the STop IMatinib trial, most of the relapses occurred within the first 6 months," Dr. Réa explained in an interview after her presentation.
"Here we didn’t have any relapses after 6 months," Dr. Réa added. "For the nine patients who didn’t relapse, the median follow-up is 10 months." The duration of time that these patients remained treatment free was between 6 months and 19 months.
For inclusion in the study, patients had to be aged 18 years or older with chronic or acute phase chronic myeloid leukemia at diagnosis, and be receiving ongoing dasatinib or nilotinib treatment after intolerance or resistance to imatinib therapy. TKI treatment had to have been administered for at least 3 years, and patients needed to have undetectable levels of BCR-ABL with at least 20,000 copies of ABL.
The primary end point was the achievement of a stable major molecular response (MMR) at 6 months, determined by monthly blood counts and real-time quantitative polymerase chain reaction for the first year of discontinuation, then every 2-3 months thereafter. Bone marrow smears and cytogenic and mutational analysis are undertaken if there is a rise in BCR-ABL above an internationally standardized (IS) ratio of 1%. Patients are re-treated with dasatinib or nilotinib if there is a loss of MMR of more than 0.1% IS.
Results showed that at 6 months’ follow-up, 71% of patients had a persistent MMR, and 64% remained treatment free. Five patients restarted TKI treatment at a median of 5 months, and four patients lost MMR after a median of 3 months. However, the patients who lost major molecular response retained their sensitivity to TKIs, and BCR-ABL was undetectable in all five patients who restarted therapy.
Asked what these results could mean for clinical practice, Dr. Réa noted that they are an early indicator that stopping treatment with second-generation TKIs will probably be an option for some patients who achieve good responses. Careful (at least monthly) follow-up of patients who cease treatment would be required, at least in the research setting.
"We don’t know, but we hope the relapse rate will be lower than we have seen with imatinib [discontinuation]," Dr. Réa said. She added, however, that there is an indication that the relapse rate could actually be higher than that seen in the STIM trial.
As yet, the optimal duration of treatment with a second-generation TKI before discontinuation can be attempted is unknown. "In the STop IMatinib trial, it seems to be between 4 and 5 years," Dr. Réa observed. "So I don’t think it will be reasonable to stop treatment before that period of time."
Further results from the trial can be expected later in the year, Dr. Réa noted. To date, 23 patients have been recruited and 8 more are to be included in the trial.
Dr. Réa disclosed serving on advisory boards of Bristol-Myers Squibb and Novartis.
LONDON – Stopping treatment with dasatinib and nilotinib might be safe in chronic myeloid leukemia patients who have achieved sustained and complete molecular responses, early data from a pilot study have shown.
The STOP 2GTKI study is a successor to the STop IMatinib (STIM) trial, which showed that stopping treatment with imatinib – the first-generation tyrosine kinase inhibitor (TKI) of BCR-ABL – could be feasible in patients who achieve long-lasting complete molecular responses (Lancet Oncol.2010;11:1029-35).
Although still preliminary, the new data suggest that it could be possible to do the same with these second-generation TKIs in patients who were previously intolerant or resistant to treatment with imatinib, Dr. Delphine Réa said at the annual Congress of the European Hematology Association.
"There are different kinds of reasons why we should aim at stopping tyrosine kinase inhibitors in chronic myeloid leukemia patients," said Dr. Réa of Hôpital Saint-Louis in Paris.
"The first one relates to patients. From the patients’ perspective it’s very important to have the hope of feeling cured," said Dr. Réa, a member of the French team that performed both the STIM and the STOP 2G-TKI studies.
Other reasons given include avoiding the adverse effects of prolonged therapy on quality of life, and reducing health care costs by steering clear of unnecessary long-term treatment for what becomes a chronic disease. It’s also important for clinicians to be able to show that a treatment really does cure a disease, she said, and the only way to do that is to stop the treatment.
Dr. Réa presented early data on 14 patients who had been enrolled in the STOP 2G-TKI pilot study until May 2011 and for whom there was at least 6 months’ follow-up. The median age of patients was 59 years.
"I think it’s very important to have 6 months’ follow-up at least because in the STop IMatinib trial, most of the relapses occurred within the first 6 months," Dr. Réa explained in an interview after her presentation.
"Here we didn’t have any relapses after 6 months," Dr. Réa added. "For the nine patients who didn’t relapse, the median follow-up is 10 months." The duration of time that these patients remained treatment free was between 6 months and 19 months.
For inclusion in the study, patients had to be aged 18 years or older with chronic or acute phase chronic myeloid leukemia at diagnosis, and be receiving ongoing dasatinib or nilotinib treatment after intolerance or resistance to imatinib therapy. TKI treatment had to have been administered for at least 3 years, and patients needed to have undetectable levels of BCR-ABL with at least 20,000 copies of ABL.
The primary end point was the achievement of a stable major molecular response (MMR) at 6 months, determined by monthly blood counts and real-time quantitative polymerase chain reaction for the first year of discontinuation, then every 2-3 months thereafter. Bone marrow smears and cytogenic and mutational analysis are undertaken if there is a rise in BCR-ABL above an internationally standardized (IS) ratio of 1%. Patients are re-treated with dasatinib or nilotinib if there is a loss of MMR of more than 0.1% IS.
Results showed that at 6 months’ follow-up, 71% of patients had a persistent MMR, and 64% remained treatment free. Five patients restarted TKI treatment at a median of 5 months, and four patients lost MMR after a median of 3 months. However, the patients who lost major molecular response retained their sensitivity to TKIs, and BCR-ABL was undetectable in all five patients who restarted therapy.
Asked what these results could mean for clinical practice, Dr. Réa noted that they are an early indicator that stopping treatment with second-generation TKIs will probably be an option for some patients who achieve good responses. Careful (at least monthly) follow-up of patients who cease treatment would be required, at least in the research setting.
"We don’t know, but we hope the relapse rate will be lower than we have seen with imatinib [discontinuation]," Dr. Réa said. She added, however, that there is an indication that the relapse rate could actually be higher than that seen in the STIM trial.
As yet, the optimal duration of treatment with a second-generation TKI before discontinuation can be attempted is unknown. "In the STop IMatinib trial, it seems to be between 4 and 5 years," Dr. Réa observed. "So I don’t think it will be reasonable to stop treatment before that period of time."
Further results from the trial can be expected later in the year, Dr. Réa noted. To date, 23 patients have been recruited and 8 more are to be included in the trial.
Dr. Réa disclosed serving on advisory boards of Bristol-Myers Squibb and Novartis.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
Major Finding: At 6 months’ follow-up, 71% of patients achieved a stable MMR, and 64% remained treatment free.
Data Source: Preliminary data on 14 patients (median age, 59 years) with chronic myeloid leukemia participating in the ongoing STOP 2G-TKI pilot study.
Disclosures: Dr. Réa disclosed serving on advisory boards of Bristol-Myers Squibb and Novartis.
Rituximab Maintenance Called "New Standard" for Mantle Cell Lymphoma
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
Major Finding: After induction therapy, rituximab-treated patients experienced a median remission of 77 months, compared with 24 months in interferon-alpha-treated patients (HR, 0.54; P = .0109).
Data Source: A 560-patient trial conducted by the European Mantle Cell Lymphoma Network in elderly patients who were subject to two randomized comparisons: 1) R-CHOP or R-FC as induction treatment; or 2) interferon or rituximab as maintenance.
Disclosures: Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
Rituximab Maintenance Called "New Standard" for Mantle Cell Lymphoma
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
Major Finding: After induction therapy, rituximab-treated patients experienced a median remission of 77 months, compared with 24 months in interferon-alpha-treated patients (HR, 0.54; P = .0109).
Data Source: A 560-patient trial conducted by the European Mantle Cell Lymphoma Network in elderly patients who were subject to two randomized comparisons: 1) R-CHOP or R-FC as induction treatment; or 2) interferon or rituximab as maintenance.
Disclosures: Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
Rituximab Maintenance Called "New Standard" for Mantle Cell Lymphoma
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
LONDON – Rituximab more than doubled the duration of remission in elderly patients with mantle cell lymphoma when used as maintenance therapy in those who had already responded to induction therapy in a large, randomized controlled trial.
First results from the European Mantle Cell Lymphoma (MCL) Network study show that rituximab maintenance is associated with a median remission of 77 months. In comparison, when interferon (IFN) was used as maintenance, the median was 24 months (hazard ratio, 0.54; P = .0109).
Overall survival data are not yet fully mature but suggest that rituximab (Rituxan in the United States, Mabthera in Europe) improves upon the rates achievable. At 4 years’ follow-up, 62% of patients treated with IFN and 77% of those maintained on rituximab were still alive. This difference was not statistically significant, however.
Rituximab is not licensed for the treatment of MCL in Europe or the United States.
"Rituximab after R-CHOP [rituximab, cyclophosphamide (Cytoxan), hydroxydaunorubicin (doxorubicin, Adriamycin), Oncovin (vincristine), and prednisolone] should become the new standard for elderly MCL patients to which new regimens should be compared," said study investigator Dr. Hanneke C. Kluin-Nelemans of the University Medical Center of Groningen, the Netherlands, while reporting the findings at the annual congress of the European Hematology Association.
"MCL is a disease of the elderly," Dr. Kluin-Nelemans observed. More than 60% of patients with MCL are aged 60 years or older, and treatment options can be limited. High-dose chemotherapy and autologous stem cell transplantation are not always possible, and "almost all patients relapse" after initial immunochemotherapy. Furthermore, overall survival is about 3-5 years in those who are aged 60 years and up, Dr. Kluin-Nelemans said.
Patients in the trial had previously received induction therapy with R-CHOP or R-FC (rituximab plus fludarabine with cyclophosphamide).
The study consisted of two randomization phases, the first of which saw 560 newly diagnosed, fit (performance status 0-2), elderly patients with MCL treated with either eight cycles of R-CHOP or six cycles of R-FC. The 310 patients who responded to either regimen entered the second randomization phase – this time to treatment with single-agent IFN or rituximab alone as maintenance therapy. IFN was given as 1-3 doses/week depending on the formulation used (IFN-alpha or peg-IFN), and rituximab (375 mg/m2) was given as a single dose every 2 months until disease progression.
The study was closed early in October 2010 under the advisement of the trial’s Data Safety Monitoring Board, as the data favored rituximab over IFN as maintenance therapy, and the R-CHOP regimen was clearly better than R-FC regimen.
Per-protocol results showed a significant improvement in remission during maintenance treatment with rituximab vs. IFN. These data remained significant in an intent-to-treat analysis.
The investigators also looked to see what effects the induction regimens could have on the maintenance phase results, and found that the duration of remission was significantly better in patients who received R-CHOP than in those given R-FC.
Dr. Kluin-Nelemans was questioned after her presentation as to that lack of a placebo-controlled arm. In response, she said that an analysis had looked at 87 of 250 patients who were not randomized to maintenance treatment. All had stopped rituximab treatment before they could be randomized, and were thus a population of patients that could potentially benefit.
Rituximab was associated with significantly less fatigue (P less than .001) and fewer infections (P less than .022), and was less likely to decrease white blood cell and platelet counts (P less than .001) than IFN. The rate of more serious infections was also lower than with IFN (P less than .022)
Considering the efficacy findings and the fact that there was also low toxicity associated with rituximab compared with IFN, these data suggest that the CD-20-targeting agent could be a better option for maintenance therapy than other biologic or immunomodulatory agents.
"We have shown it’s possible to do a large [randomized controlled trial] with two randomization steps in fit, elderly patients with MCL," Dr. Kluin-Nelemans said. "Rituximab more than doubles the remission duration in patients depending upon initial therapy."
Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.
FROM THE ANNUAL CONGRESS OF THE EUROPEAN HEMATOLOGY ASSOCIATION
Major Finding: After induction therapy, rituximab-treated patients experienced a median remission of 77 months, compared with 24 months in interferon-alpha-treated patients (HR, 0.54; P = .0109).
Data Source: A 560-patient trial conducted by the European Mantle Cell Lymphoma Network in elderly patients who were subject to two randomized comparisons: 1) R-CHOP or R-FC as induction treatment; or 2) interferon or rituximab as maintenance.
Disclosures: Dr. Kluin-Nelemans stated that she had no conflicts of interest related to her presentation.