Lymphoma & Plasma Cell Disorders

Two variations of the BCL2 gene are linked with the survival prospects of patients with diffuse large B-cell lymphoma (DLBCL) who are treated with the R-CHOP regimen, based on a study published in Haematologica.

In the population-based, case-control study of patients with non-Hodgkin’s lymphoma across the British Columbia province, Morteza Bashash, PhD, of the Dalla Lana School of Public Health, Toronto, and researchers at the British Columbia Cancer Agency analyzed 217 germline DLBCL samples, excluding those with primary mediastinal large B-cell lymphoma, specifically looking at nine single nucleotide polymorphisms (SNPs).

Nephron/Wikimedia Commons/CC BY-SA 3.0 ecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

Two variations of the BCL2 gene are linked with the survival prospects of patients with diffuse large B-cell lymphoma (DLBCL) who are treated with the R-CHOP regimen, based on a study published in Haematologica.

In the population-based, case-control study of patients with non-Hodgkin’s lymphoma across the British Columbia province, Morteza Bashash, PhD, of the Dalla Lana School of Public Health, Toronto, and researchers at the British Columbia Cancer Agency analyzed 217 germline DLBCL samples, excluding those with primary mediastinal large B-cell lymphoma, specifically looking at nine single nucleotide polymorphisms (SNPs).

Nephron/Wikimedia Commons/CC BY-SA 3.0 ecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

Two variations of the BCL2 gene are linked with the survival prospects of patients with diffuse large B-cell lymphoma (DLBCL) who are treated with the R-CHOP regimen, based on a study published in Haematologica.

In the population-based, case-control study of patients with non-Hodgkin’s lymphoma across the British Columbia province, Morteza Bashash, PhD, of the Dalla Lana School of Public Health, Toronto, and researchers at the British Columbia Cancer Agency analyzed 217 germline DLBCL samples, excluding those with primary mediastinal large B-cell lymphoma, specifically looking at nine single nucleotide polymorphisms (SNPs).

Nephron/Wikimedia Commons/CC BY-SA 3.0 ecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

Photo © ASCO/Danny Morton 2017

Ibrutinib, the Bruton’s tyrosine kinase (BTK) inhibitor, has transformed the treatment landscape for patients with relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL).

Yet for patients with high-risk molecular features, such as 11q deletion, 17p deletion, or TP53 mutation, relapse remains problematic.

Investigators evaluated whether the addition of ublituximab to ibrutinib would improve the outcome of patients with genetically high-risk CLL in the GENUINE (UTX-IB-301) phase 3 study.

Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center in Springfield, Oregon, reported the results at the 2017 ASCO Annual Meeting (abstract 7504).*

Ublituximab is a glycoengineered, anti-CD20 type 1 monoclonal antibody that maintains complement-dependent cytotoxicity and enhances antibody-dependent cell-mediated cytotoxicity. In a phase 2 study in combination with ibrutinib, it achieved an ORR of approximately 88%.

Protocol design

Originally, the study had co-primary endpoints of overall response rate (ORR) and progression-free survival (PFS). To adequately power for both endpoints, the target enrollment was 330 patients.

Dr Sharman explained that after 22 months of open enrollment, the trial sponsor determined that the original enrollment goal could not be met in a timely manner and elected to redesign the protocol.

In the modified protocol, ORR became the primary response rate and PFS a secondary endpoint. This allowed for a reduced target enrollment of 120. However, the study was no longer powered to detect a change in PFS.

Investigators stratified the patients by lines of prior therapy and then randomized them to receive ibrutinib or ublituximab plus ibrutinib.

The ibrutinib dose was 420 mg daily in both arms. Ublituximab dose was 900 mg on days 1, 8, and 15 of cycle 1, day 1 of cycles 2 through 6 and every third cycle thereafter.

The primary endpoint was ORR as assessed by Independent Central Review (IRC) using the iwCLL 2008 criteria.

Secondary endpoints included PFS, the complete response (CR) rate and depth of response (minimal residual disease [MRD] negativity), and safety.

The investigators assessed patients for response on weeks 8, 16, 24, and every 12 weeks thereafter.

The primary endpoint was evaluated when all enrolled patients had at least 2 efficacy evaluations.

The median follow-up was 11.4 months.

 Patient characteristics

 Patients with relapsed or refractory high-risk CLL had their disease centrally confirmed for the presence of deletion 17p, deletion 11q, and/or TP53 mutation.

They had measurable disease, ECOG performance status of 2 or less, no history of transformation of CLL, and no prior BTK inhibitor therapy.

 The investigators randomized 126 patients, and 117 received any dose of therapy.

“The dropout was because in part ibrutinib was via commercial supply and not every patient could get access,” Dr Sharman noted.

Fifty-nine patients were treated in the combination arm and 58 in the monotherapy arm.

All patients had at least one of the specified mutations, which were relatively balanced between the 2 arms.

Patients were a mean age of 67 (range, 43 – 87), had a median of 3 prior therapies (range, 1 – 8), and more than 70% were male.

Patient characteristics were similar in each arm except for bulky disease, with 45% in the combination arm having bulky disease of 5 cm or more at baseline, compared with 26% in the monotherapy arm.

Twenty percent of the patients were considered refractory to rituximab.

Safety

Infusion reactions occurred in 54% of patients in the combination arm and 5% had grade 3/4 reactions. None occurred in the ibrutinib arm, since the latter is an orally bioavailable drug.

Other adverse events of all grades occurring in 10% of patients or more for the combination and monotherapy arms, respectively, were: diarrhea (42% and 40%), fatigue (27% and 33%), insomnia (24% and 10%), nausea (22% and 21%), headache (20% and 28%), arthralgia (19% and 17%), cough (19% and 24%), abdominal pain (15% and 9%), stomatitis (15% and 9%), upper respiratory infection (15% and 12%), dizziness (15% and 22%), contusion (15% and 29%), anemia (14% and 17%), and peripheral edema (10% and 21%).

Neutropenia was higher in the experimental arm, 22% any grade, compared with 12% in the ibrutinib arm, although grade 3 or higher neutropenia was similar in the 2 arms. Other laboratory abnormalities were similar between the arms.

Efficacy

 The best ORR in the combination arm was 78%, with 7% achieving CR compared with 45% in the monotherapy arm with no CRs (P<0.001).

Nineteen percent of the combination arm achieved MRD negativity in peripheral blood compared with 2% of the monotherapy arm (P<0.01).

The reduction in lymph node size was similar between the arms.

In contrast, lymphocytosis was very different between the arms.

“As has been reported multiple times with targeted B-cell receptor signaling inhibitors,” Dr Sharman said, “patients treated with ibrutinib experienced rapid increase in their lymphocytes, returning approximately to baseline by 3 months and decreasing thereafter.”

“By contrast,” he continued, “those patients treated with the additional antibody had much more rapid resolution of their lymphocytosis. This was true whether patients were considered rituximab refractory or not.”

The investigators performed an additional analysis of ORR, this time including patients who achieved partial response with lymphocytosis (PR-L). These patients were not included in the primary endpoint because the iwCLL 2008 criteria had not yet been updated to include PR-L.

The best overall response including active PR-L patients was 83% in the experimental arm and 59% in the ibrutinib monotherapy arm (P<0.01).

PFS showed a trend toward improvement in the patients treated with the combination, with a hazard ratio of 0.559, which was not of statistical significance at the time of analysis.

The investigators concluded that the study met its primary endpoint, with a greater response rate and a greater depth of response than ibrutinib alone.

And the addition of ublituximab did not alter the safety profile of ibrutinib monotherapy.

TG Therapeutics, Inc, funded the study. 

*Data in the abstract differ from the meeting presentation.

Photo © ASCO/Danny Morton 2017

Ibrutinib, the Bruton’s tyrosine kinase (BTK) inhibitor, has transformed the treatment landscape for patients with relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL).

Yet for patients with high-risk molecular features, such as 11q deletion, 17p deletion, or TP53 mutation, relapse remains problematic.

Investigators evaluated whether the addition of ublituximab to ibrutinib would improve the outcome of patients with genetically high-risk CLL in the GENUINE (UTX-IB-301) phase 3 study.

Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center in Springfield, Oregon, reported the results at the 2017 ASCO Annual Meeting (abstract 7504).*

Ublituximab is a glycoengineered, anti-CD20 type 1 monoclonal antibody that maintains complement-dependent cytotoxicity and enhances antibody-dependent cell-mediated cytotoxicity. In a phase 2 study in combination with ibrutinib, it achieved an ORR of approximately 88%.

Protocol design

Originally, the study had co-primary endpoints of overall response rate (ORR) and progression-free survival (PFS). To adequately power for both endpoints, the target enrollment was 330 patients.

Dr Sharman explained that after 22 months of open enrollment, the trial sponsor determined that the original enrollment goal could not be met in a timely manner and elected to redesign the protocol.

In the modified protocol, ORR became the primary response rate and PFS a secondary endpoint. This allowed for a reduced target enrollment of 120. However, the study was no longer powered to detect a change in PFS.

Investigators stratified the patients by lines of prior therapy and then randomized them to receive ibrutinib or ublituximab plus ibrutinib.

The ibrutinib dose was 420 mg daily in both arms. Ublituximab dose was 900 mg on days 1, 8, and 15 of cycle 1, day 1 of cycles 2 through 6 and every third cycle thereafter.

The primary endpoint was ORR as assessed by Independent Central Review (IRC) using the iwCLL 2008 criteria.

Secondary endpoints included PFS, the complete response (CR) rate and depth of response (minimal residual disease [MRD] negativity), and safety.

The investigators assessed patients for response on weeks 8, 16, 24, and every 12 weeks thereafter.

The primary endpoint was evaluated when all enrolled patients had at least 2 efficacy evaluations.

The median follow-up was 11.4 months.

 Patient characteristics

 Patients with relapsed or refractory high-risk CLL had their disease centrally confirmed for the presence of deletion 17p, deletion 11q, and/or TP53 mutation.

They had measurable disease, ECOG performance status of 2 or less, no history of transformation of CLL, and no prior BTK inhibitor therapy.

 The investigators randomized 126 patients, and 117 received any dose of therapy.

“The dropout was because in part ibrutinib was via commercial supply and not every patient could get access,” Dr Sharman noted.

Fifty-nine patients were treated in the combination arm and 58 in the monotherapy arm.

All patients had at least one of the specified mutations, which were relatively balanced between the 2 arms.

Patients were a mean age of 67 (range, 43 – 87), had a median of 3 prior therapies (range, 1 – 8), and more than 70% were male.

Patient characteristics were similar in each arm except for bulky disease, with 45% in the combination arm having bulky disease of 5 cm or more at baseline, compared with 26% in the monotherapy arm.

Twenty percent of the patients were considered refractory to rituximab.

Safety

Infusion reactions occurred in 54% of patients in the combination arm and 5% had grade 3/4 reactions. None occurred in the ibrutinib arm, since the latter is an orally bioavailable drug.

Other adverse events of all grades occurring in 10% of patients or more for the combination and monotherapy arms, respectively, were: diarrhea (42% and 40%), fatigue (27% and 33%), insomnia (24% and 10%), nausea (22% and 21%), headache (20% and 28%), arthralgia (19% and 17%), cough (19% and 24%), abdominal pain (15% and 9%), stomatitis (15% and 9%), upper respiratory infection (15% and 12%), dizziness (15% and 22%), contusion (15% and 29%), anemia (14% and 17%), and peripheral edema (10% and 21%).

Neutropenia was higher in the experimental arm, 22% any grade, compared with 12% in the ibrutinib arm, although grade 3 or higher neutropenia was similar in the 2 arms. Other laboratory abnormalities were similar between the arms.

Efficacy

 The best ORR in the combination arm was 78%, with 7% achieving CR compared with 45% in the monotherapy arm with no CRs (P<0.001).

Nineteen percent of the combination arm achieved MRD negativity in peripheral blood compared with 2% of the monotherapy arm (P<0.01).

The reduction in lymph node size was similar between the arms.

In contrast, lymphocytosis was very different between the arms.

“As has been reported multiple times with targeted B-cell receptor signaling inhibitors,” Dr Sharman said, “patients treated with ibrutinib experienced rapid increase in their lymphocytes, returning approximately to baseline by 3 months and decreasing thereafter.”

“By contrast,” he continued, “those patients treated with the additional antibody had much more rapid resolution of their lymphocytosis. This was true whether patients were considered rituximab refractory or not.”

The investigators performed an additional analysis of ORR, this time including patients who achieved partial response with lymphocytosis (PR-L). These patients were not included in the primary endpoint because the iwCLL 2008 criteria had not yet been updated to include PR-L.

The best overall response including active PR-L patients was 83% in the experimental arm and 59% in the ibrutinib monotherapy arm (P<0.01).

PFS showed a trend toward improvement in the patients treated with the combination, with a hazard ratio of 0.559, which was not of statistical significance at the time of analysis.

The investigators concluded that the study met its primary endpoint, with a greater response rate and a greater depth of response than ibrutinib alone.

And the addition of ublituximab did not alter the safety profile of ibrutinib monotherapy.

TG Therapeutics, Inc, funded the study. 

*Data in the abstract differ from the meeting presentation.

Photo © ASCO/Danny Morton 2017

Ibrutinib, the Bruton’s tyrosine kinase (BTK) inhibitor, has transformed the treatment landscape for patients with relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL).

Yet for patients with high-risk molecular features, such as 11q deletion, 17p deletion, or TP53 mutation, relapse remains problematic.

Investigators evaluated whether the addition of ublituximab to ibrutinib would improve the outcome of patients with genetically high-risk CLL in the GENUINE (UTX-IB-301) phase 3 study.

Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center in Springfield, Oregon, reported the results at the 2017 ASCO Annual Meeting (abstract 7504).*

Ublituximab is a glycoengineered, anti-CD20 type 1 monoclonal antibody that maintains complement-dependent cytotoxicity and enhances antibody-dependent cell-mediated cytotoxicity. In a phase 2 study in combination with ibrutinib, it achieved an ORR of approximately 88%.

Protocol design

Originally, the study had co-primary endpoints of overall response rate (ORR) and progression-free survival (PFS). To adequately power for both endpoints, the target enrollment was 330 patients.

Dr Sharman explained that after 22 months of open enrollment, the trial sponsor determined that the original enrollment goal could not be met in a timely manner and elected to redesign the protocol.

In the modified protocol, ORR became the primary response rate and PFS a secondary endpoint. This allowed for a reduced target enrollment of 120. However, the study was no longer powered to detect a change in PFS.

Investigators stratified the patients by lines of prior therapy and then randomized them to receive ibrutinib or ublituximab plus ibrutinib.

The ibrutinib dose was 420 mg daily in both arms. Ublituximab dose was 900 mg on days 1, 8, and 15 of cycle 1, day 1 of cycles 2 through 6 and every third cycle thereafter.

The primary endpoint was ORR as assessed by Independent Central Review (IRC) using the iwCLL 2008 criteria.

Secondary endpoints included PFS, the complete response (CR) rate and depth of response (minimal residual disease [MRD] negativity), and safety.

The investigators assessed patients for response on weeks 8, 16, 24, and every 12 weeks thereafter.

The primary endpoint was evaluated when all enrolled patients had at least 2 efficacy evaluations.

The median follow-up was 11.4 months.

 Patient characteristics

 Patients with relapsed or refractory high-risk CLL had their disease centrally confirmed for the presence of deletion 17p, deletion 11q, and/or TP53 mutation.

They had measurable disease, ECOG performance status of 2 or less, no history of transformation of CLL, and no prior BTK inhibitor therapy.

 The investigators randomized 126 patients, and 117 received any dose of therapy.

“The dropout was because in part ibrutinib was via commercial supply and not every patient could get access,” Dr Sharman noted.

Fifty-nine patients were treated in the combination arm and 58 in the monotherapy arm.

All patients had at least one of the specified mutations, which were relatively balanced between the 2 arms.

Patients were a mean age of 67 (range, 43 – 87), had a median of 3 prior therapies (range, 1 – 8), and more than 70% were male.

Patient characteristics were similar in each arm except for bulky disease, with 45% in the combination arm having bulky disease of 5 cm or more at baseline, compared with 26% in the monotherapy arm.

Twenty percent of the patients were considered refractory to rituximab.

Safety

Infusion reactions occurred in 54% of patients in the combination arm and 5% had grade 3/4 reactions. None occurred in the ibrutinib arm, since the latter is an orally bioavailable drug.

Other adverse events of all grades occurring in 10% of patients or more for the combination and monotherapy arms, respectively, were: diarrhea (42% and 40%), fatigue (27% and 33%), insomnia (24% and 10%), nausea (22% and 21%), headache (20% and 28%), arthralgia (19% and 17%), cough (19% and 24%), abdominal pain (15% and 9%), stomatitis (15% and 9%), upper respiratory infection (15% and 12%), dizziness (15% and 22%), contusion (15% and 29%), anemia (14% and 17%), and peripheral edema (10% and 21%).

Neutropenia was higher in the experimental arm, 22% any grade, compared with 12% in the ibrutinib arm, although grade 3 or higher neutropenia was similar in the 2 arms. Other laboratory abnormalities were similar between the arms.

Efficacy

 The best ORR in the combination arm was 78%, with 7% achieving CR compared with 45% in the monotherapy arm with no CRs (P<0.001).

Nineteen percent of the combination arm achieved MRD negativity in peripheral blood compared with 2% of the monotherapy arm (P<0.01).

The reduction in lymph node size was similar between the arms.

In contrast, lymphocytosis was very different between the arms.

“As has been reported multiple times with targeted B-cell receptor signaling inhibitors,” Dr Sharman said, “patients treated with ibrutinib experienced rapid increase in their lymphocytes, returning approximately to baseline by 3 months and decreasing thereafter.”

“By contrast,” he continued, “those patients treated with the additional antibody had much more rapid resolution of their lymphocytosis. This was true whether patients were considered rituximab refractory or not.”

The investigators performed an additional analysis of ORR, this time including patients who achieved partial response with lymphocytosis (PR-L). These patients were not included in the primary endpoint because the iwCLL 2008 criteria had not yet been updated to include PR-L.

The best overall response including active PR-L patients was 83% in the experimental arm and 59% in the ibrutinib monotherapy arm (P<0.01).

PFS showed a trend toward improvement in the patients treated with the combination, with a hazard ratio of 0.559, which was not of statistical significance at the time of analysis.

The investigators concluded that the study met its primary endpoint, with a greater response rate and a greater depth of response than ibrutinib alone.

And the addition of ublituximab did not alter the safety profile of ibrutinib monotherapy.

TG Therapeutics, Inc, funded the study. 

*Data in the abstract differ from the meeting presentation.

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo © ASCO/Danny Morton 2017

CHICAGO—The 15-year cumulative incidence of severe health conditions for survivors of childhood cancer has decreased over the past 30 years, from 12.7% for those diagnosed in the 1970s to 10.1% and 8.9% for those diagnosed in the 1980s and 1990s, respectively. And the decreases were greatest for patients with Wilms’ tumor and Hodgkin lymphoma (HL), followed by patients with astrocytoma, non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL).

Investigators of the Childhood Cancer Survivor Study (CCSS) undertook a retrospective cohort analysis of children aged 0 – 14 years diagnosed with cancer between 1970 and 1999. Their goal was to determine whether cancer therapy modifications have maintained cure rates while decreasing the risk of late effects of therapy.

Todd M. Gibson, PhD, of St Jude Children’s Research Hospital in Memphis, Tennessee, presented the findings at the 2017 annual meeting of the American Society for Clinical Oncology (ASCO) as abstract LBA10500.

Researchers analyzed data from 23,600 childhood cancer survivors in the CCSS who were alive 5 years after diagnosis. The patients had leukemia, lymphoma, CNS malignancies, Wilms tumor, neuroblastoma, or soft-tissue/bone sarcoma.

Dr Gibson noted that while 83% of children with a malignancy achieve a 5-year survival, more than half develop at least one severe, disabling, life-threatening health condition by age 50.

The survivors were a median age at last follow-up of 28 years (range, 5-63) and the median time since diagnosis was 21 years (range, 5-43).

The investigators found significant decreases in severe health conditions in 6 diagnostic groups:

• Wilms tumor, decreased from 13% to 5% (P<0.0001)
• HL, decreased from 18% to 11% (P<0.0001)
• Astrocytoma, decreased from 15% to 9% (P=0.004)
• NHL, decreased from 10% to 6% (P=0.04)
• ALL, decreased from 9% to 7% (P=0.002)
• Ewings sarcoma, decreased from 19% to 10% (P=0.01)

They found no reductions in subsequent severe health conditions among survivors of neuroblastoma, acute myeloid leukemia (AML), soft tissue sarcoma, or osteosarcoma.

The investigators believe the decreases were driven mainly by a reduced incidence of endocrine conditions, subsequent malignant neoplasms, gastrointestinal and neurological conditions, but not cardiac or pulmonary conditions.

They also analyzed the reduction in treatment intensities by decade for different diseases and found they correlated with the reduced incidence of serious chronic health conditions by 15 years after diagnosis.

The National Institutes of Health funded the study.

Photo courtesy of the CDC

A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4^th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.

The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.

The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.

For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.

In the treatment of FN, the panel added a 4^th-generation cephalosporin as empirical therapy in high-risk FN.

The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.

The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients.  GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.

The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.

Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.

The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.

The panel's recommendations and their rationale can be found in the JCO article.

The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.

Photo courtesy of the CDC

A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4^th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.

The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.

The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.

For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.

In the treatment of FN, the panel added a 4^th-generation cephalosporin as empirical therapy in high-risk FN.

The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.

The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients.  GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.

The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.

Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.

The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.

The panel's recommendations and their rationale can be found in the JCO article.

The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.

Photo courtesy of the CDC

A multidisciplinary, international panel of experts has updated earlier clinical practice guidelines on managing fever and neutropenia (FN) in children with cancer and in those undergoing hematopoietic stem cell transplantation (HSCT). And while most of the recommendations remained unchanged from the 2012 guidelines, a few key differences emerged. The changes included addition of a 4^th generation cephalosporin for empirical antifungal therapy and refinements in risk stratification for invasive fungal disease (IFD), among others.

The new guidelines were published by The International Pediatric Fever and Neutropenia Guideline Panel in the Journal of Clinical Oncology.

The recommendations were organized into 3 major sections: initial presentation, ongoing management, and empirical antifungal therapy. The guidelines panel followed procedures previously validated for creating evidence-based guidelines and used the Appraisal of Guidelines for Research & Evaluation II instrument as a framework.

For the initial presentation of FN, the panel increased the quality of evidence from low to moderate in the recommendation to obtain peripheral blood cultures concurrent with central venous catheter cultures.

In the treatment of FN, the panel added a 4^th-generation cephalosporin as empirical therapy in high-risk FN.

The panel refined the IFD risk factors and decreased the quality of evidence from moderate to low. Children with acute myeloid leukemia (AML), high-risk acute lymphoblastic leukemia (ALL), relapsed acute leukemia, those undergoing allogeneic HSCT, those with prolonged neutropenia, and those receiving high-dose corticosteroids are at high risk of IFD. All others should be categorized as IFD low risk.

The panel suggested serum galactomannan not be used to guide empirical antifungal management for prolonged FN lasting 96 hours or more in high-risk IFD patients.  GM does not rule out non-Aspergillus molds, and therefore high negative values provide less useful predictions. Previously, the use of galactomannan was a weak recommendation.

The panel added a new recommendation against using fungal polymerase chain reaction (PCR) testing in blood. They explained PCR testing provides poor positive predictive values and negative predictive values are not sufficiently high to be clinically useful. Also, PCR testing is not yet standardized.

Another new recommendation is the addition of imaging of the abdomen in patients without localizing signs or symptoms. Even though the ideal imaging modality is not known, ultrasound is readily available, not associated with radiation exposure, and usually does not require sedation. For these reasons, the panel said it is preferable to computed tomography or magnetic resonance imaging.

The panel also changed a previously weak recommendation to administer empirical therapy for IFD low-risk patients with prolonged FN to a weak recommendation against administering therapy for these patients.

The panel's recommendations and their rationale can be found in the JCO article.

The guidelines update was supported by meeting grants from the Canadian Institutes of Health Research and the Garron Comprehensive Cancer Centre.

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for axicabtagene ciloleucel (formerly KTE-C19), a chimeric antigen receptor (CAR) T-cell therapy.

Kite Pharma, Inc. is seeking approval for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory, aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA has set a review deadline of November 29, 2017, for the axicabtagene ciloleucel BLA.

Axicabtagene ciloleucel also has breakthrough therapy designation from the FDA as a treatment for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.

ZUMA-1 trial

The BLA for axicabtagene ciloleucel is supported by data from the phase 2 ZUMA-1 trial, which enrolled 111 patients with relapsed/refractory B-cell NHL.

After a single infusion of axicabtagene ciloleucel, the objective response rate was 82%. At a median follow-up of 8.7 months, 44% of patients were still in response, which included 39% of patients in complete response.

The most common grade 3 or higher adverse events were anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

There were 3 deaths during the trial that were not due to disease progression. Two of these deaths were deemed related to axicabtagene ciloleucel. 

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for axicabtagene ciloleucel (formerly KTE-C19), a chimeric antigen receptor (CAR) T-cell therapy.

Kite Pharma, Inc. is seeking approval for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory, aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA has set a review deadline of November 29, 2017, for the axicabtagene ciloleucel BLA.

Axicabtagene ciloleucel also has breakthrough therapy designation from the FDA as a treatment for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.

ZUMA-1 trial

The BLA for axicabtagene ciloleucel is supported by data from the phase 2 ZUMA-1 trial, which enrolled 111 patients with relapsed/refractory B-cell NHL.

After a single infusion of axicabtagene ciloleucel, the objective response rate was 82%. At a median follow-up of 8.7 months, 44% of patients were still in response, which included 39% of patients in complete response.

The most common grade 3 or higher adverse events were anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

There were 3 deaths during the trial that were not due to disease progression. Two of these deaths were deemed related to axicabtagene ciloleucel. 

Diffuse large B-cell lymphoma

The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for axicabtagene ciloleucel (formerly KTE-C19), a chimeric antigen receptor (CAR) T-cell therapy.

Kite Pharma, Inc. is seeking approval for axicabtagene ciloleucel as a treatment for patients with relapsed or refractory, aggressive non-Hodgkin lymphoma (NHL) who are ineligible for autologous stem cell transplant.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA has set a review deadline of November 29, 2017, for the axicabtagene ciloleucel BLA.

Axicabtagene ciloleucel also has breakthrough therapy designation from the FDA as a treatment for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma.

ZUMA-1 trial

The BLA for axicabtagene ciloleucel is supported by data from the phase 2 ZUMA-1 trial, which enrolled 111 patients with relapsed/refractory B-cell NHL.

After a single infusion of axicabtagene ciloleucel, the objective response rate was 82%. At a median follow-up of 8.7 months, 44% of patients were still in response, which included 39% of patients in complete response.

The most common grade 3 or higher adverse events were anemia (43%), neutropenia (39%), decreased neutrophil count (32%), febrile neutropenia (31%), decreased white blood cell count (29%), thrombocytopenia (24%), encephalopathy (21%), and decreased lymphocyte count (20%).

There were 3 deaths during the trial that were not due to disease progression. Two of these deaths were deemed related to axicabtagene ciloleucel. 

mycosis fungoides

The European Commission (EC) has granted orphan designation to MRG-106 for the treatment of cutaneous T-cell lymphoma (CTCL).

MRG-106 is a locked nucleic acid-modified oligonucleotide inhibitor of miR-155-5p.

miRagen Therapeutics, Inc., the company developing MRG-106, is currently testing the drug in a phase 1 trial of CTCL patients.

Early results from this trial were presented at the 2016 ASH Annual Meeting.

Researchers presented results in 6 patients with stage I-III mycosis fungoides.

The patients received 4 or 5 intratumoral injections of MRG-106 (at 75 mg) over 2 weeks. Four patients received saline injections in a second lesion on the same schedule.

There were 3 adverse events related to MRG-106—pain during injection, burning sensation during injection, and tingling at the injection site.

Adverse events considered possibly related to MRG-106 were pruritus, erythema, skin inflammation, sore on hand, nausea, decrease in white blood cells, neutropenia, and prolonged partial thromboplastin time.

One patient was taken off the trial due to rapid disease progression. The other 5 patients completed the dosing period.

All 5 patients had a reduction in the baseline Composite Assessment of Index Lesion Severity score in MRG-106-treated and saline-treated lesions.

The average maximal reduction was 55% (range, 33% to 77%) in MRG-106-treated lesions and 39% (range, 13% to 75%) in saline-treated lesions.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

mycosis fungoides

The European Commission (EC) has granted orphan designation to MRG-106 for the treatment of cutaneous T-cell lymphoma (CTCL).

MRG-106 is a locked nucleic acid-modified oligonucleotide inhibitor of miR-155-5p.

miRagen Therapeutics, Inc., the company developing MRG-106, is currently testing the drug in a phase 1 trial of CTCL patients.

Early results from this trial were presented at the 2016 ASH Annual Meeting.

Researchers presented results in 6 patients with stage I-III mycosis fungoides.

The patients received 4 or 5 intratumoral injections of MRG-106 (at 75 mg) over 2 weeks. Four patients received saline injections in a second lesion on the same schedule.

There were 3 adverse events related to MRG-106—pain during injection, burning sensation during injection, and tingling at the injection site.

Adverse events considered possibly related to MRG-106 were pruritus, erythema, skin inflammation, sore on hand, nausea, decrease in white blood cells, neutropenia, and prolonged partial thromboplastin time.

One patient was taken off the trial due to rapid disease progression. The other 5 patients completed the dosing period.

All 5 patients had a reduction in the baseline Composite Assessment of Index Lesion Severity score in MRG-106-treated and saline-treated lesions.

The average maximal reduction was 55% (range, 33% to 77%) in MRG-106-treated lesions and 39% (range, 13% to 75%) in saline-treated lesions.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

mycosis fungoides

The European Commission (EC) has granted orphan designation to MRG-106 for the treatment of cutaneous T-cell lymphoma (CTCL).

MRG-106 is a locked nucleic acid-modified oligonucleotide inhibitor of miR-155-5p.

miRagen Therapeutics, Inc., the company developing MRG-106, is currently testing the drug in a phase 1 trial of CTCL patients.

Early results from this trial were presented at the 2016 ASH Annual Meeting.

Researchers presented results in 6 patients with stage I-III mycosis fungoides.

The patients received 4 or 5 intratumoral injections of MRG-106 (at 75 mg) over 2 weeks. Four patients received saline injections in a second lesion on the same schedule.

There were 3 adverse events related to MRG-106—pain during injection, burning sensation during injection, and tingling at the injection site.

Adverse events considered possibly related to MRG-106 were pruritus, erythema, skin inflammation, sore on hand, nausea, decrease in white blood cells, neutropenia, and prolonged partial thromboplastin time.

One patient was taken off the trial due to rapid disease progression. The other 5 patients completed the dosing period.

All 5 patients had a reduction in the baseline Composite Assessment of Index Lesion Severity score in MRG-106-treated and saline-treated lesions.

The average maximal reduction was 55% (range, 33% to 77%) in MRG-106-treated lesions and 39% (range, 13% to 75%) in saline-treated lesions.

About orphan designation

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.

The European Medicines Agency adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the EC for a final decision. The EC typically makes a decision within 30 days of that submission. 

Photo courtesy of the CDC

New research provides an explanation for the fact that US patients with hematologic malignancies are less likely to enroll in hospice care than patients with solid tumor malignancies.

Results of a national survey suggest that concerns about the adequacy of hospice may prevent hematologic oncologists from referring their patients.

Researchers say this finding, published in Cancer, points to potential means of improving end-of-life care for patients with hematologic malignancies.

Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues carried out this study.

The team conducted a survey of a national sample of hematologic oncologists listed in the publicly available clinical directory of the American Society of Hematology.

More than 57% of physicians who were contacted provided responses, for a total of 349 respondents.

The survey included questions about views regarding the helpfulness and adequacy of home hospice services for patients with hematologic malignancies, as well as factors that would impact oncologists’ likelihood of referring patients to hospice.

More than 68% of hematologic oncologists strongly agreed that hospice care is “helpful” for patients with hematologic malignancies.

However, 46% of the oncologists felt that home hospice is “inadequate” for the needs of patients with hematologic malignancies, when compared to inpatient hospice.

Still, most of the respondents who believed home hospice is inadequate said they would be more likely to refer patients if platelet and red blood cell transfusions were readily available.

“Our findings are important as they shed light on factors that are potential barriers to hospice referrals,” Dr Odejide said. “These findings can be employed to develop targeted interventions to address hospice underuse for patients with blood cancers.” 

Photo courtesy of the CDC

New research provides an explanation for the fact that US patients with hematologic malignancies are less likely to enroll in hospice care than patients with solid tumor malignancies.

Results of a national survey suggest that concerns about the adequacy of hospice may prevent hematologic oncologists from referring their patients.

Researchers say this finding, published in Cancer, points to potential means of improving end-of-life care for patients with hematologic malignancies.

Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues carried out this study.

The team conducted a survey of a national sample of hematologic oncologists listed in the publicly available clinical directory of the American Society of Hematology.

More than 57% of physicians who were contacted provided responses, for a total of 349 respondents.

The survey included questions about views regarding the helpfulness and adequacy of home hospice services for patients with hematologic malignancies, as well as factors that would impact oncologists’ likelihood of referring patients to hospice.

More than 68% of hematologic oncologists strongly agreed that hospice care is “helpful” for patients with hematologic malignancies.

However, 46% of the oncologists felt that home hospice is “inadequate” for the needs of patients with hematologic malignancies, when compared to inpatient hospice.

Still, most of the respondents who believed home hospice is inadequate said they would be more likely to refer patients if platelet and red blood cell transfusions were readily available.

“Our findings are important as they shed light on factors that are potential barriers to hospice referrals,” Dr Odejide said. “These findings can be employed to develop targeted interventions to address hospice underuse for patients with blood cancers.” 

Photo courtesy of the CDC

New research provides an explanation for the fact that US patients with hematologic malignancies are less likely to enroll in hospice care than patients with solid tumor malignancies.

Results of a national survey suggest that concerns about the adequacy of hospice may prevent hematologic oncologists from referring their patients.

Researchers say this finding, published in Cancer, points to potential means of improving end-of-life care for patients with hematologic malignancies.

Oreofe Odejide, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues carried out this study.

The team conducted a survey of a national sample of hematologic oncologists listed in the publicly available clinical directory of the American Society of Hematology.

More than 57% of physicians who were contacted provided responses, for a total of 349 respondents.

The survey included questions about views regarding the helpfulness and adequacy of home hospice services for patients with hematologic malignancies, as well as factors that would impact oncologists’ likelihood of referring patients to hospice.

More than 68% of hematologic oncologists strongly agreed that hospice care is “helpful” for patients with hematologic malignancies.

However, 46% of the oncologists felt that home hospice is “inadequate” for the needs of patients with hematologic malignancies, when compared to inpatient hospice.

Still, most of the respondents who believed home hospice is inadequate said they would be more likely to refer patients if platelet and red blood cell transfusions were readily available.

“Our findings are important as they shed light on factors that are potential barriers to hospice referrals,” Dr Odejide said. “These findings can be employed to develop targeted interventions to address hospice underuse for patients with blood cancers.” 

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

Photo courtesy of NIH

A global study has revealed inequity of access to and quality of healthcare among and within countries and suggests people are dying from causes with well-known treatments.

“What we have found about healthcare access and quality is disturbing,” said Christopher Murray, MD, DPhil, of the University of Washington in Seattle.

“Having a strong economy does not guarantee good healthcare. Having great medical technology doesn’t either. We know this because people are not getting the care that should be expected for diseases with established treatments.”

Dr Murray and his colleagues reported these findings in The Lancet.

For this study, the researchers assessed access to and quality of healthcare services in 195 countries from 1990 to 2015.

The group used the Healthcare Access and Quality Index, a summary measure based on 32 causes* that, in the presence of high-quality healthcare, should not result in death. Leukemia and Hodgkin lymphoma are among these causes.

Countries were assigned scores for each of the causes, based on estimates from the annual Global Burden of Diseases, Injuries, and Risk Factors study (GBD), a systematic, scientific effort to quantify the magnitude of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

In addition, data were extracted from the most recent GBD update and evaluated using a Socio-demographic Index based on rates of education, fertility, and income.

Results

The 195 countries were assigned scores on a scale of 1 to 100 for healthcare access and quality. They received scores for the 32 causes as well as overall scores.

In 2015, the top-ranked nation was Andorra, with an overall score of 95. Its lowest treatment score was 70, for Hodgkin lymphoma.

The lowest-ranked nation was Central African Republic, with a score of 29. Its highest treatment score was 65, for diphtheria.

Nations in much of sub-Saharan Africa, as well as in south Asia and several countries in Latin America and the Caribbean, also had low rankings.

However, many countries in these regions, including China (score: 74) and Ethiopia (score: 44), have seen sizeable gains since 1990.

‘Developed’ nations falling short

The US had an overall score of 81 (in 2015), tied with Estonia and Montenegro. As with many other nations, the US scored 100 in treating common vaccine-preventable diseases, such as diphtheria, tetanus, and measles.

However, the US had 9 treatment categories in which it scored in the 60s: lower respiratory infections (60), neonatal disorders (69), non-melanoma skin cancer (68), Hodgkin lymphoma (67), ischemic heart disease (62), hypertensive heart disease (64), diabetes (67), chronic kidney disease (62), and the adverse effects of medical treatment itself (68).

“America’s ranking is an embarrassment, especially considering the US spends more than $9000 per person on healthcare annually, more than any other country,” Dr Murray said.

“Anyone with a stake in the current healthcare debate, including elected officials at the federal, state, and local levels, should take a look at where the US is falling short.”

Other nations with strong economies and advanced medical technology are falling short in some areas as well.

For example, Norway and Australia each scored 90 overall, among the highest in the world. However, Norway scored 65 in its treatment for testicular cancer, and Australia scored 52 for treating non-melanoma skin cancer.

“In the majority of cases, both of these cancers can be treated effectively,” Dr Murray said. “Shouldn’t it cause serious concern that people are dying of these causes in countries that have the resources to address them?” 

*The 32 causes are:

1. Adverse effects of medical treatment
2. Appendicitis
3. Breast cancer
4. Cerebrovascular disease (stroke)
5. Cervical cancer
6. Chronic kidney disease
7. Chronic respiratory diseases
8. Colon and rectum cancer
9. Congenital anomalies
10. Diabetes mellitus
11. Diarrhea-related diseases
12. Diphtheria
13. Epilepsy
14. Gallbladder and biliary diseases
15. Hodgkin lymphoma
16. Hypertensive heart disease
17. Inguinal, femoral, and abdominal hernia
18. Ischemic heart disease
19. Leukemia
20. Lower respiratory infections
21. Maternal disorders
22. Measles
23. Neonatal disorders
24. Non-melanoma skin cancer
25. Peptic ulcer disease
26. Rheumatic heart disease
27. Testicular cancer
28. Tetanus
29. Tuberculosis
30. Upper respiratory infections
31. Uterine cancer
32. Whooping cough.

The peripheral blood absolute lymphocyte-to-monocyte ratio (ALC/AMC) was prognostic for overall survival in mantle cell lymphoma patients who have undergone induction therapy, based on a retrospective review study of 96 patients by Andre Goy, MD, of John Theurer Cancer Center, Hackensack (NJ) University, and his colleagues.

Overall survival was better when ALC/AMC was 2 or greater following induction therapy, the researchers wrote in an abstract published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The finding indicates that novel maintenance programs, including targeting the microenvironment or immune response, might be appropriate when patients with mantle cell lymphoma have low ALC/AMC.

The researchers examined data for 96 consecutive mantle cell lymphoma patients. The ALC/AMC was determined from peripheral blood counts obtained approximately 30 days following completion of initial therapy or immediately prior to stem cell mobilization in patients who had first line stem cell transplants.

The ALC/AMC was less than 2 in 67 patients and was 2 or greater in 29 patients. The two patient cohorts were similar in median age, ethnicities, stage distributions, elevated beta-2-microglobulin, elevated lactate dehydrogenate, and Mantle Cell Lymphoma International Prognostic Index scores.

ALC/AMC was less than 2 in 10 of 13 transplanted patients and in 57 of 83 patients who did not undergo transplants. At a median follow-up of 43 months, the median overall survival has not been reached in either cohort.

The 5-year survival rate was 90% among patients with an ALC/AMC of 2 or greater and 68% in those with an ALC/AMC less than 2 (log-rank P less than .05).

Similar ALC/AMC 5-year survival trends were noted when subsetting to the 25 patients with high risk Mantle Cell Lymphoma International Prognostic Index scores (72% vs. 45%; P = .07).

Dr. Goy disclosed honoraria from Acerta Pharma, Celgene, Pharmacyclics, and Takeda; a consulting or advisory role with Acerta Pharma, Celgene, Infinity Pharmaceuticals, Pharmacyclics, and Takeda; and speakers’ bureaus participation for Pharmacyclics and Takeda.

Prognostic value of the absolute lymphocyte-to-monocyte (ALC/AMC) ratio on overall survival among patients with mantle cell lymphoma. Published in conjunction with the 2017 ASCO Annual Meeting. Abstract No: e19030.

mdales@frontlinemedcom.com

On Twitter @maryjodales

The peripheral blood absolute lymphocyte-to-monocyte ratio (ALC/AMC) was prognostic for overall survival in mantle cell lymphoma patients who have undergone induction therapy, based on a retrospective review study of 96 patients by Andre Goy, MD, of John Theurer Cancer Center, Hackensack (NJ) University, and his colleagues.

Overall survival was better when ALC/AMC was 2 or greater following induction therapy, the researchers wrote in an abstract published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The finding indicates that novel maintenance programs, including targeting the microenvironment or immune response, might be appropriate when patients with mantle cell lymphoma have low ALC/AMC.

The researchers examined data for 96 consecutive mantle cell lymphoma patients. The ALC/AMC was determined from peripheral blood counts obtained approximately 30 days following completion of initial therapy or immediately prior to stem cell mobilization in patients who had first line stem cell transplants.

The ALC/AMC was less than 2 in 67 patients and was 2 or greater in 29 patients. The two patient cohorts were similar in median age, ethnicities, stage distributions, elevated beta-2-microglobulin, elevated lactate dehydrogenate, and Mantle Cell Lymphoma International Prognostic Index scores.

ALC/AMC was less than 2 in 10 of 13 transplanted patients and in 57 of 83 patients who did not undergo transplants. At a median follow-up of 43 months, the median overall survival has not been reached in either cohort.

The 5-year survival rate was 90% among patients with an ALC/AMC of 2 or greater and 68% in those with an ALC/AMC less than 2 (log-rank P less than .05).

Similar ALC/AMC 5-year survival trends were noted when subsetting to the 25 patients with high risk Mantle Cell Lymphoma International Prognostic Index scores (72% vs. 45%; P = .07).

Dr. Goy disclosed honoraria from Acerta Pharma, Celgene, Pharmacyclics, and Takeda; a consulting or advisory role with Acerta Pharma, Celgene, Infinity Pharmaceuticals, Pharmacyclics, and Takeda; and speakers’ bureaus participation for Pharmacyclics and Takeda.

Prognostic value of the absolute lymphocyte-to-monocyte (ALC/AMC) ratio on overall survival among patients with mantle cell lymphoma. Published in conjunction with the 2017 ASCO Annual Meeting. Abstract No: e19030.

mdales@frontlinemedcom.com

On Twitter @maryjodales

The peripheral blood absolute lymphocyte-to-monocyte ratio (ALC/AMC) was prognostic for overall survival in mantle cell lymphoma patients who have undergone induction therapy, based on a retrospective review study of 96 patients by Andre Goy, MD, of John Theurer Cancer Center, Hackensack (NJ) University, and his colleagues.

Overall survival was better when ALC/AMC was 2 or greater following induction therapy, the researchers wrote in an abstract published in conjunction with the annual meeting of the American Society of Clinical Oncology.

The finding indicates that novel maintenance programs, including targeting the microenvironment or immune response, might be appropriate when patients with mantle cell lymphoma have low ALC/AMC.

The researchers examined data for 96 consecutive mantle cell lymphoma patients. The ALC/AMC was determined from peripheral blood counts obtained approximately 30 days following completion of initial therapy or immediately prior to stem cell mobilization in patients who had first line stem cell transplants.

The ALC/AMC was less than 2 in 67 patients and was 2 or greater in 29 patients. The two patient cohorts were similar in median age, ethnicities, stage distributions, elevated beta-2-microglobulin, elevated lactate dehydrogenate, and Mantle Cell Lymphoma International Prognostic Index scores.

ALC/AMC was less than 2 in 10 of 13 transplanted patients and in 57 of 83 patients who did not undergo transplants. At a median follow-up of 43 months, the median overall survival has not been reached in either cohort.

The 5-year survival rate was 90% among patients with an ALC/AMC of 2 or greater and 68% in those with an ALC/AMC less than 2 (log-rank P less than .05).

Similar ALC/AMC 5-year survival trends were noted when subsetting to the 25 patients with high risk Mantle Cell Lymphoma International Prognostic Index scores (72% vs. 45%; P = .07).

Dr. Goy disclosed honoraria from Acerta Pharma, Celgene, Pharmacyclics, and Takeda; a consulting or advisory role with Acerta Pharma, Celgene, Infinity Pharmaceuticals, Pharmacyclics, and Takeda; and speakers’ bureaus participation for Pharmacyclics and Takeda.

Prognostic value of the absolute lymphocyte-to-monocyte (ALC/AMC) ratio on overall survival among patients with mantle cell lymphoma. Published in conjunction with the 2017 ASCO Annual Meeting. Abstract No: e19030.

mdales@frontlinemedcom.com

On Twitter @maryjodales