User login
Study: Many cancer patients don’t understand clinical trials
MADRID—Results of a nationwide study suggest many cancer patients in Ireland don’t understand key aspects of clinical trial methodology.
Most of the patients surveyed, which included individuals who had participated in a clinical trial, did not understand the concepts of randomization or equipoise.
“Over half of previous medical trial participants and 73% of those who had never been on a cancer clinical trial did not understand that, in a randomized trial, the treatment given was decided by chance,” said study investigator Catherine Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, Ireland.
“We also found that most patients did not understand clinical equipoise—the fact that no one knows which treatment is best. Surprisingly, this was more marked in previous clinical trial participants, 60% of whom believed that their doctor would know which study arm was best.”
Dr Kelly and her colleagues presented these findings at the ESMO 2017 Congress (abstract 1465P_PR).
The researchers surveyed 1090 adult cancer patients treated at 1 of 14 participating oncology centers across Ireland.
The patients’ median age was 60 (range, 50-69), 64.4% were female, and 66% were diagnosed between 2014 and 2016. The most common cancer types were breast (31.4%), colorectal (15.6%), hematologic (12.6%), genitourinary (11.6%), and lung (6.8%).
The patients filled out anonymized questionnaires in which they were asked to evaluate statements about clinical trials. The patients had to determine whether a statement is true or false, or they could indicate that they didn’t know an answer.
A majority of the patients (82.3%) said they understood what a medical or cancer clinical trial is. And 27.8% of patients said they had previously participated in a cancer trial.
However, many patients didn’t know when clinical trials may be an option. Twenty-two percent of patients said it is true that “clinical trials are only used when standard treatments have not worked,” and 26.6% said they didn’t know if this statement is true or false.
Roughly a third (33.5%) of patients said it is true that, in a randomized trial, treatment is decided by chance, but 41.4% of patients said this is false, and 25% said they didn’t know.
More than half of patients (56.5%) said their doctor would know which treatment was superior in a clinical trial, and 23.2% of patients said they didn’t know if their doctor would know.
About 61% of all patients said their doctor would make sure they received the superior treatment in a clinical trial. An even greater percentage—63.6%—of patients who had previously participated in a clinical trial said the same.
“To provide informed consent when participating in a trial, patients need to understand these key concepts, and doctors explaining them well is essential to alleviating any fears that might prevent patients from participating,” Dr Kelly said.
“Doctors have a responsibility to properly inform their patients in this regard because they are the ones patients trust the most. As we analyze the data further, we will be able to offer physicians a more detailed picture of the questions patients need answered and the factors that influence their decision-making according to age group, cancer type, educational background, and other demographics.”
Funding for this research was provided to Cancer Trials Ireland by Amgen, Abbvie, Bayor, and Inveva. 
MADRID—Results of a nationwide study suggest many cancer patients in Ireland don’t understand key aspects of clinical trial methodology.
Most of the patients surveyed, which included individuals who had participated in a clinical trial, did not understand the concepts of randomization or equipoise.
“Over half of previous medical trial participants and 73% of those who had never been on a cancer clinical trial did not understand that, in a randomized trial, the treatment given was decided by chance,” said study investigator Catherine Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, Ireland.
“We also found that most patients did not understand clinical equipoise—the fact that no one knows which treatment is best. Surprisingly, this was more marked in previous clinical trial participants, 60% of whom believed that their doctor would know which study arm was best.”
Dr Kelly and her colleagues presented these findings at the ESMO 2017 Congress (abstract 1465P_PR).
The researchers surveyed 1090 adult cancer patients treated at 1 of 14 participating oncology centers across Ireland.
The patients’ median age was 60 (range, 50-69), 64.4% were female, and 66% were diagnosed between 2014 and 2016. The most common cancer types were breast (31.4%), colorectal (15.6%), hematologic (12.6%), genitourinary (11.6%), and lung (6.8%).
The patients filled out anonymized questionnaires in which they were asked to evaluate statements about clinical trials. The patients had to determine whether a statement is true or false, or they could indicate that they didn’t know an answer.
A majority of the patients (82.3%) said they understood what a medical or cancer clinical trial is. And 27.8% of patients said they had previously participated in a cancer trial.
However, many patients didn’t know when clinical trials may be an option. Twenty-two percent of patients said it is true that “clinical trials are only used when standard treatments have not worked,” and 26.6% said they didn’t know if this statement is true or false.
Roughly a third (33.5%) of patients said it is true that, in a randomized trial, treatment is decided by chance, but 41.4% of patients said this is false, and 25% said they didn’t know.
More than half of patients (56.5%) said their doctor would know which treatment was superior in a clinical trial, and 23.2% of patients said they didn’t know if their doctor would know.
About 61% of all patients said their doctor would make sure they received the superior treatment in a clinical trial. An even greater percentage—63.6%—of patients who had previously participated in a clinical trial said the same.
“To provide informed consent when participating in a trial, patients need to understand these key concepts, and doctors explaining them well is essential to alleviating any fears that might prevent patients from participating,” Dr Kelly said.
“Doctors have a responsibility to properly inform their patients in this regard because they are the ones patients trust the most. As we analyze the data further, we will be able to offer physicians a more detailed picture of the questions patients need answered and the factors that influence their decision-making according to age group, cancer type, educational background, and other demographics.”
Funding for this research was provided to Cancer Trials Ireland by Amgen, Abbvie, Bayor, and Inveva.
MADRID—Results of a nationwide study suggest many cancer patients in Ireland don’t understand key aspects of clinical trial methodology.
Most of the patients surveyed, which included individuals who had participated in a clinical trial, did not understand the concepts of randomization or equipoise.
“Over half of previous medical trial participants and 73% of those who had never been on a cancer clinical trial did not understand that, in a randomized trial, the treatment given was decided by chance,” said study investigator Catherine Kelly, MB BCh, of Mater Misericordiae University Hospital in Dublin, Ireland.
“We also found that most patients did not understand clinical equipoise—the fact that no one knows which treatment is best. Surprisingly, this was more marked in previous clinical trial participants, 60% of whom believed that their doctor would know which study arm was best.”
Dr Kelly and her colleagues presented these findings at the ESMO 2017 Congress (abstract 1465P_PR).
The researchers surveyed 1090 adult cancer patients treated at 1 of 14 participating oncology centers across Ireland.
The patients’ median age was 60 (range, 50-69), 64.4% were female, and 66% were diagnosed between 2014 and 2016. The most common cancer types were breast (31.4%), colorectal (15.6%), hematologic (12.6%), genitourinary (11.6%), and lung (6.8%).
The patients filled out anonymized questionnaires in which they were asked to evaluate statements about clinical trials. The patients had to determine whether a statement is true or false, or they could indicate that they didn’t know an answer.
A majority of the patients (82.3%) said they understood what a medical or cancer clinical trial is. And 27.8% of patients said they had previously participated in a cancer trial.
However, many patients didn’t know when clinical trials may be an option. Twenty-two percent of patients said it is true that “clinical trials are only used when standard treatments have not worked,” and 26.6% said they didn’t know if this statement is true or false.
Roughly a third (33.5%) of patients said it is true that, in a randomized trial, treatment is decided by chance, but 41.4% of patients said this is false, and 25% said they didn’t know.
More than half of patients (56.5%) said their doctor would know which treatment was superior in a clinical trial, and 23.2% of patients said they didn’t know if their doctor would know.
About 61% of all patients said their doctor would make sure they received the superior treatment in a clinical trial. An even greater percentage—63.6%—of patients who had previously participated in a clinical trial said the same.
“To provide informed consent when participating in a trial, patients need to understand these key concepts, and doctors explaining them well is essential to alleviating any fears that might prevent patients from participating,” Dr Kelly said.
“Doctors have a responsibility to properly inform their patients in this regard because they are the ones patients trust the most. As we analyze the data further, we will be able to offer physicians a more detailed picture of the questions patients need answered and the factors that influence their decision-making according to age group, cancer type, educational background, and other demographics.”
Funding for this research was provided to Cancer Trials Ireland by Amgen, Abbvie, Bayor, and Inveva.
CCSs have higher burden of chronic conditions
Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.
The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.
“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.
The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.
At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).
The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).
The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.
For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.
And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.
“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.
“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”
Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.
The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.
“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.
The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.
At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).
The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).
The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.
For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.
And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.
“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.
“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”
Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.
The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.
“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.
The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.
At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).
The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).
The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.
For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.
And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.
“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.
“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”
FDA places full, partial holds on durvalumab trials
The US Food and Drug Administration (FDA) has placed a partial clinical hold on 5 trials and a full clinical hold on 1 trial of the anti-PD-L1 antibody durvalumab (Imfinzi™).
In these trials, researchers are testing durvalumab in combination with immunomodulatory and chemotherapy agents in patients with multiple myeloma (MM) and lymphomas.
At present, no new patients can be enrolled in any of the 6 trials.
Patients enrolled in the trials on partial clinical hold can remain on treatment if they are receiving clinical benefit.
Patients enrolled in the trial on full clinical hold will discontinue the study treatment.
The FDA’s decision to place these trials on hold is related to risks identified in trials studying another anti-PD-1 agent, pembrolizumab, in MM patients.
Data from the pembrolizumab trials indicate the risks outweigh the benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.
In addition, there may be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.
With this in mind, the FDA placed the MEDI4736-MM-002 trial on full clinical hold.
MEDI4736-MM-002 is a phase 1b study designed to determine the recommended dose and regimen of durvalumab in combination with lenalidomide, with and without low-dose dexamethasone, in patients with newly diagnosed MM.
The FDA also placed the following trials on partial clinical hold:
- MEDI4736-MM-001: A phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide, with or without low-dose dexamethasone, in patients with relapsed and refractory MM
- MEDI4736-MM-003: A phase 2 study to determine the safety and efficacy of the combination of durvalumab and daratumumab in patients with relapsed and refractory MM
- MEDI4736-MM-005: A phase 2 study to determine the efficacy of the combination of durvalumab plus daratumumab in patients with relapsed and refractory MM who have progressed while on a current treatment regimen containing daratumumab
- MEDI4736-NHL-001: A phase 1/2 study to assess the safety and tolerability of durvalumab as monotherapy and in combination therapy in patients with lymphomas, including chronic lymphocytic leukemia. The only arm in this trial for which enrollment is suspended is the arm with the durvalumab, lenalidomide, and rituximab combination.
- MEDI4736-DLBCL-001: A phase 2 study to evaluate the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or with lenalidomide plus R-CHOP in patients with previously untreated, high-risk diffuse large B-cell lymphoma.
The trials that will continue to enroll are:
- MEDI4736-MDS-001: A phase 2 study evaluating the efficacy and safety of subcutaneous azacitidine in combination with durvalumab in previously untreated patients with higher-risk myelodysplastic syndromes or in elderly (≥65 years) acute myeloid leukemia patients not eligible for hematopoietic stem cell transplant
- CC-486-MDS-006: A phase 2 study to evaluate the efficacy and safety of CC-486 alone or in combination with durvalumab in patients with myelodysplastic syndromes who fail to achieve an objective response to treatment with azacitidine for injection or decitabine.
Durvalumab is being developed by Celgene Corporation and MedImmune, the global biologics research and development arm of AstraZeneca.
The use of durvalumab in combination with other agents for the treatment of patients with hematologic malignancies is not approved by the FDA, and the safety and efficacy of those combinations has not been established.
Durvalumab has accelerated approval from the FDA to treat patients with locally advanced or metastatic urothelial carcinoma.
The US Food and Drug Administration (FDA) has placed a partial clinical hold on 5 trials and a full clinical hold on 1 trial of the anti-PD-L1 antibody durvalumab (Imfinzi™).
In these trials, researchers are testing durvalumab in combination with immunomodulatory and chemotherapy agents in patients with multiple myeloma (MM) and lymphomas.
At present, no new patients can be enrolled in any of the 6 trials.
Patients enrolled in the trials on partial clinical hold can remain on treatment if they are receiving clinical benefit.
Patients enrolled in the trial on full clinical hold will discontinue the study treatment.
The FDA’s decision to place these trials on hold is related to risks identified in trials studying another anti-PD-1 agent, pembrolizumab, in MM patients.
Data from the pembrolizumab trials indicate the risks outweigh the benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.
In addition, there may be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.
With this in mind, the FDA placed the MEDI4736-MM-002 trial on full clinical hold.
MEDI4736-MM-002 is a phase 1b study designed to determine the recommended dose and regimen of durvalumab in combination with lenalidomide, with and without low-dose dexamethasone, in patients with newly diagnosed MM.
The FDA also placed the following trials on partial clinical hold:
- MEDI4736-MM-001: A phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide, with or without low-dose dexamethasone, in patients with relapsed and refractory MM
- MEDI4736-MM-003: A phase 2 study to determine the safety and efficacy of the combination of durvalumab and daratumumab in patients with relapsed and refractory MM
- MEDI4736-MM-005: A phase 2 study to determine the efficacy of the combination of durvalumab plus daratumumab in patients with relapsed and refractory MM who have progressed while on a current treatment regimen containing daratumumab
- MEDI4736-NHL-001: A phase 1/2 study to assess the safety and tolerability of durvalumab as monotherapy and in combination therapy in patients with lymphomas, including chronic lymphocytic leukemia. The only arm in this trial for which enrollment is suspended is the arm with the durvalumab, lenalidomide, and rituximab combination.
- MEDI4736-DLBCL-001: A phase 2 study to evaluate the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or with lenalidomide plus R-CHOP in patients with previously untreated, high-risk diffuse large B-cell lymphoma.
The trials that will continue to enroll are:
- MEDI4736-MDS-001: A phase 2 study evaluating the efficacy and safety of subcutaneous azacitidine in combination with durvalumab in previously untreated patients with higher-risk myelodysplastic syndromes or in elderly (≥65 years) acute myeloid leukemia patients not eligible for hematopoietic stem cell transplant
- CC-486-MDS-006: A phase 2 study to evaluate the efficacy and safety of CC-486 alone or in combination with durvalumab in patients with myelodysplastic syndromes who fail to achieve an objective response to treatment with azacitidine for injection or decitabine.
Durvalumab is being developed by Celgene Corporation and MedImmune, the global biologics research and development arm of AstraZeneca.
The use of durvalumab in combination with other agents for the treatment of patients with hematologic malignancies is not approved by the FDA, and the safety and efficacy of those combinations has not been established.
Durvalumab has accelerated approval from the FDA to treat patients with locally advanced or metastatic urothelial carcinoma.
The US Food and Drug Administration (FDA) has placed a partial clinical hold on 5 trials and a full clinical hold on 1 trial of the anti-PD-L1 antibody durvalumab (Imfinzi™).
In these trials, researchers are testing durvalumab in combination with immunomodulatory and chemotherapy agents in patients with multiple myeloma (MM) and lymphomas.
At present, no new patients can be enrolled in any of the 6 trials.
Patients enrolled in the trials on partial clinical hold can remain on treatment if they are receiving clinical benefit.
Patients enrolled in the trial on full clinical hold will discontinue the study treatment.
The FDA’s decision to place these trials on hold is related to risks identified in trials studying another anti-PD-1 agent, pembrolizumab, in MM patients.
Data from the pembrolizumab trials indicate the risks outweigh the benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.
In addition, there may be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.
With this in mind, the FDA placed the MEDI4736-MM-002 trial on full clinical hold.
MEDI4736-MM-002 is a phase 1b study designed to determine the recommended dose and regimen of durvalumab in combination with lenalidomide, with and without low-dose dexamethasone, in patients with newly diagnosed MM.
The FDA also placed the following trials on partial clinical hold:
- MEDI4736-MM-001: A phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide, with or without low-dose dexamethasone, in patients with relapsed and refractory MM
- MEDI4736-MM-003: A phase 2 study to determine the safety and efficacy of the combination of durvalumab and daratumumab in patients with relapsed and refractory MM
- MEDI4736-MM-005: A phase 2 study to determine the efficacy of the combination of durvalumab plus daratumumab in patients with relapsed and refractory MM who have progressed while on a current treatment regimen containing daratumumab
- MEDI4736-NHL-001: A phase 1/2 study to assess the safety and tolerability of durvalumab as monotherapy and in combination therapy in patients with lymphomas, including chronic lymphocytic leukemia. The only arm in this trial for which enrollment is suspended is the arm with the durvalumab, lenalidomide, and rituximab combination.
- MEDI4736-DLBCL-001: A phase 2 study to evaluate the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or with lenalidomide plus R-CHOP in patients with previously untreated, high-risk diffuse large B-cell lymphoma.
The trials that will continue to enroll are:
- MEDI4736-MDS-001: A phase 2 study evaluating the efficacy and safety of subcutaneous azacitidine in combination with durvalumab in previously untreated patients with higher-risk myelodysplastic syndromes or in elderly (≥65 years) acute myeloid leukemia patients not eligible for hematopoietic stem cell transplant
- CC-486-MDS-006: A phase 2 study to evaluate the efficacy and safety of CC-486 alone or in combination with durvalumab in patients with myelodysplastic syndromes who fail to achieve an objective response to treatment with azacitidine for injection or decitabine.
Durvalumab is being developed by Celgene Corporation and MedImmune, the global biologics research and development arm of AstraZeneca.
The use of durvalumab in combination with other agents for the treatment of patients with hematologic malignancies is not approved by the FDA, and the safety and efficacy of those combinations has not been established.
Durvalumab has accelerated approval from the FDA to treat patients with locally advanced or metastatic urothelial carcinoma.
FDA grants orphan designation to product for CMV
The US Food and Drug Administration (FDA) has granted orphan drug designation to ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ATA230 for the treatment of cytomegalovirus (CMV) viremia and disease in immunocompromised patients.
ATA230 is an allogeneic, cytotoxic T-lymphocyte (CTL) product targeting antigens expressed by CMV.
The product is under investigation in phase 2 trials of patients with CMV viremia and disease who are refractory or resistant to antiviral treatment.
Atara Biotherapeutics, Inc., the company developing ATA230, said it will evaluate development plans for this therapy with the FDA and other global health authorities after beginning phase 3 studies of another product, ATA129.
The company said it decided to prioritize ATA129, which is being developed to treat patients with Epstein-Barr-virus-associated post-transplant lymphoproliferative disorder.
Phase 2 trial of ATA230
Researchers reported phase 2 results with ATA230 at the 2016 ASH Annual Meeting.
The data encompassed 15 patients with documented CMV mutations conferring resistance to antiviral therapies. The patients had received a median of 3 prior therapies.
Eleven of the 15 patients (73.3%) responded to ATA230, 6 with complete responses and 5 with partial responses.
At 6 months, the overall survival was 72.7% in responders and 25% in non-responders.
Within the 6 months of follow-up, 1 of the 11 responders died of CMV, and 3 of the 4 non-responders died of CMV.
Adverse events occurred in 6 patients. One grade 3 event and 1 grade 4 event were considered possibly related to ATA230.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
FDA grants orphan designation to product for GVHD
The US Food and Drug Administration (FDA) has granted orphan drug designation to ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to ApoGraft™ as prophylaxis for acute and chronic graft-versus-host disease (GVHD) in transplant recipients.
ApoGraft is a mobilized peripheral blood cell product collected via apheresis from a matched, related donor. The product is exposed to the apoptotic mediator Fas ligand prior to transplantation.
ApoGraft was designed to eliminate immune responses after transplantation of foreign cells and tissues.
ApoGraft is being developed by Cellect Biotechnology Ltd.
The company is testing ApoGraft as acute GVHD prophylaxis in a phase 1/2 trial.
The trial is currently enrolling patients with hemato-oncology disorders who are eligible for allogeneic, HLA-matched hematopoietic stem cell transplant (HSCT).
The study is expected to have 4 cohorts, each consisting of 3 patients.
The difference between the cohorts is the amount of apoptotic mediator Fas ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT:
- 10 ng/mL APO010 in Cohort 1
- 25 ng/mL APO010 in Cohort 2
- 50 ng/mL APO010 in Cohort 3
- 100 ng/mL APO010 in Cohort 4.
The study is expected to progress from one cohort to the next based on an independent data safety monitoring board review and analysis of safety data.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
Nanocarriers could treat leukemia, lymphoma and improve HSCT
Researchers say they have created nanoparticles loaded with messenger RNA (mRNA) that can give cells the ability to fight cancers and other diseases.
To use these freeze-dried nanocarriers, the team added water and introduced the resulting mixture to cells.
The nanocarriers were able to target T cells and hematopoietic stem cells (HSCs), delivering mRNA directly to the cells and triggering short-term gene expression.
The T cells were then able to fight leukemia and lymphoma in vitro and in vivo. And the HSCs demonstrated improvements in growth and regenerative potential.
Matthias Stephan, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Nature Communications.
“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Dr Stephan said.
The researchers surrounded the nanocarrier with a negatively charged envelope with a targeting ligand attached to the surface so the carrier homes and binds to a particular cell type. When this happens, the cell engulfs the carrier, which can be loaded with different types of manmade mRNA.
The researchers mixed the freeze-dried nanocarriers with water and samples of cells. Within 4 hours, cells started showing signs that editing had taken effect.
The team noted that boosters can be given if needed. And the nanocarriers are made from a dissolving biomaterial, so they are removed from the body like other cell waste.
Testing the carriers
Dr Stephan and his colleagues tested their nanocarriers in 3 ways.
First, the researchers tested nanoparticles carrying a gene-editing tool to T cells that snipped out their natural T-cell receptors and was paired with genes encoding a chimeric antigen receptor (CAR).
The resulting CAR T cells maintained their ability to proliferate and successfully eliminated leukemia cells.
Next, the researchers tested nanocarriers targeted to CAR T cells and containing foxo1 mRNA. This prompted the T cells to develop into a type of memory cell with enhanced antitumor activity.
The team found these CAR T cells induced “substantial disease regression” and prolonged survival in a mouse model of B-cell lymphoma.
Finally, the researchers tested nanocarriers targeted to HSCs. The carriers were equipped with mRNA that “induced key regulators of self-renewal,” accelerating the growth and regenerative potential of the HSCs in vitro.
Future possibilities
Dr Stephan and his colleagues noted that these nanocarriers are built on existing technology and can be used by individuals without knowledge of nanotechnology. Therefore, the team hopes the nanocarriers will be an off-the-shelf way for cell-therapy engineers to develop new approaches to treat diseases.
The researchers believe the nanocarriers could replace electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. The team noted that up to 60 times more cells survive the introduction of the nanocarriers than survive electroporation.
“You can imagine taking the nanoparticles, injecting them into a patient, and then you don’t have to culture cells at all anymore,” Dr Stephan said.
He is now looking for commercial partners to move the technology toward additional applications and into clinical trials.
Researchers say they have created nanoparticles loaded with messenger RNA (mRNA) that can give cells the ability to fight cancers and other diseases.
To use these freeze-dried nanocarriers, the team added water and introduced the resulting mixture to cells.
The nanocarriers were able to target T cells and hematopoietic stem cells (HSCs), delivering mRNA directly to the cells and triggering short-term gene expression.
The T cells were then able to fight leukemia and lymphoma in vitro and in vivo. And the HSCs demonstrated improvements in growth and regenerative potential.
Matthias Stephan, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Nature Communications.
“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Dr Stephan said.
The researchers surrounded the nanocarrier with a negatively charged envelope with a targeting ligand attached to the surface so the carrier homes and binds to a particular cell type. When this happens, the cell engulfs the carrier, which can be loaded with different types of manmade mRNA.
The researchers mixed the freeze-dried nanocarriers with water and samples of cells. Within 4 hours, cells started showing signs that editing had taken effect.
The team noted that boosters can be given if needed. And the nanocarriers are made from a dissolving biomaterial, so they are removed from the body like other cell waste.
Testing the carriers
Dr Stephan and his colleagues tested their nanocarriers in 3 ways.
First, the researchers tested nanoparticles carrying a gene-editing tool to T cells that snipped out their natural T-cell receptors and was paired with genes encoding a chimeric antigen receptor (CAR).
The resulting CAR T cells maintained their ability to proliferate and successfully eliminated leukemia cells.
Next, the researchers tested nanocarriers targeted to CAR T cells and containing foxo1 mRNA. This prompted the T cells to develop into a type of memory cell with enhanced antitumor activity.
The team found these CAR T cells induced “substantial disease regression” and prolonged survival in a mouse model of B-cell lymphoma.
Finally, the researchers tested nanocarriers targeted to HSCs. The carriers were equipped with mRNA that “induced key regulators of self-renewal,” accelerating the growth and regenerative potential of the HSCs in vitro.
Future possibilities
Dr Stephan and his colleagues noted that these nanocarriers are built on existing technology and can be used by individuals without knowledge of nanotechnology. Therefore, the team hopes the nanocarriers will be an off-the-shelf way for cell-therapy engineers to develop new approaches to treat diseases.
The researchers believe the nanocarriers could replace electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. The team noted that up to 60 times more cells survive the introduction of the nanocarriers than survive electroporation.
“You can imagine taking the nanoparticles, injecting them into a patient, and then you don’t have to culture cells at all anymore,” Dr Stephan said.
He is now looking for commercial partners to move the technology toward additional applications and into clinical trials.
Researchers say they have created nanoparticles loaded with messenger RNA (mRNA) that can give cells the ability to fight cancers and other diseases.
To use these freeze-dried nanocarriers, the team added water and introduced the resulting mixture to cells.
The nanocarriers were able to target T cells and hematopoietic stem cells (HSCs), delivering mRNA directly to the cells and triggering short-term gene expression.
The T cells were then able to fight leukemia and lymphoma in vitro and in vivo. And the HSCs demonstrated improvements in growth and regenerative potential.
Matthias Stephan, MD, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Nature Communications.
“We developed a nanocarrier that binds and condenses synthetic mRNA and protects it from degradation,” Dr Stephan said.
The researchers surrounded the nanocarrier with a negatively charged envelope with a targeting ligand attached to the surface so the carrier homes and binds to a particular cell type. When this happens, the cell engulfs the carrier, which can be loaded with different types of manmade mRNA.
The researchers mixed the freeze-dried nanocarriers with water and samples of cells. Within 4 hours, cells started showing signs that editing had taken effect.
The team noted that boosters can be given if needed. And the nanocarriers are made from a dissolving biomaterial, so they are removed from the body like other cell waste.
Testing the carriers
Dr Stephan and his colleagues tested their nanocarriers in 3 ways.
First, the researchers tested nanoparticles carrying a gene-editing tool to T cells that snipped out their natural T-cell receptors and was paired with genes encoding a chimeric antigen receptor (CAR).
The resulting CAR T cells maintained their ability to proliferate and successfully eliminated leukemia cells.
Next, the researchers tested nanocarriers targeted to CAR T cells and containing foxo1 mRNA. This prompted the T cells to develop into a type of memory cell with enhanced antitumor activity.
The team found these CAR T cells induced “substantial disease regression” and prolonged survival in a mouse model of B-cell lymphoma.
Finally, the researchers tested nanocarriers targeted to HSCs. The carriers were equipped with mRNA that “induced key regulators of self-renewal,” accelerating the growth and regenerative potential of the HSCs in vitro.
Future possibilities
Dr Stephan and his colleagues noted that these nanocarriers are built on existing technology and can be used by individuals without knowledge of nanotechnology. Therefore, the team hopes the nanocarriers will be an off-the-shelf way for cell-therapy engineers to develop new approaches to treat diseases.
The researchers believe the nanocarriers could replace electroporation, a multistep cell-manufacturing technique that requires specialized equipment and clean rooms. The team noted that up to 60 times more cells survive the introduction of the nanocarriers than survive electroporation.
“You can imagine taking the nanoparticles, injecting them into a patient, and then you don’t have to culture cells at all anymore,” Dr Stephan said.
He is now looking for commercial partners to move the technology toward additional applications and into clinical trials.
Young cancer patients want more digital support, survey says
A recent survey of young cancer patients in the UK revealed their desire for additional digital oncology resources.
The survey showed that many of the patients already used digital resources to access information about their cancer.
However, many also expressed a need for additional resources such as online counseling or psychological support.
Esha Abrol, of Camden and Islington NHS Foundation Trust in London, UK, and her colleagues reported these findings in the Journal of Cancer Survivorship.
The researchers surveyed 102 cancer patients, ages 13 to 24, about digital media use.
The patients reported having active digital lives, with 41.6% of them rating digital resources as “essential” to their lives.
The patients reported using a variety of healthcare-related digital resources to access information about their disease, including independent sources and ones recommended to them by the professional team treating them.
Half (51%) of respondents said they kept in contact through digital means with other patients they had met during treatment. Twelve percent contacted others or started new digital relationships with people they had never met in person.
However, most of the patients were still most likely to get information about their treatment from professionals in a face-to-face environment, such as when visiting their doctor.
“This is a reassuring and appropriate finding, as this is the conventional means by which teenage and young adult oncology care is delivered by the multidisciplinary team, whether the young people choose to engage or not,” Abrol said.
At the same time, many survey respondents expressed a desire for virtual online groups (54.3%), online counseling or psychological support (43.5%), and the ability to receive (66.3%) and share (48.9%) clinical information online.
Young adults (ages 19 to 24) were more interested than adolescents (ages 13 to 18) in online counseling options and preferred receiving clinical information online.
The researchers said this may reflect young adults’ greater independence, resilience, breadth of experience in the digital world, and confidence in discussing clinical matters online.
Abrol believes these preliminary results can help inform the development of local, national, and global services to teenagers and young adults with cancer to address their unmet needs.
“These digital support resources have the potential to improve patient experience and engagement for an important subsection of teenagers and young people treated for cancer,” Abrol said.
A recent survey of young cancer patients in the UK revealed their desire for additional digital oncology resources.
The survey showed that many of the patients already used digital resources to access information about their cancer.
However, many also expressed a need for additional resources such as online counseling or psychological support.
Esha Abrol, of Camden and Islington NHS Foundation Trust in London, UK, and her colleagues reported these findings in the Journal of Cancer Survivorship.
The researchers surveyed 102 cancer patients, ages 13 to 24, about digital media use.
The patients reported having active digital lives, with 41.6% of them rating digital resources as “essential” to their lives.
The patients reported using a variety of healthcare-related digital resources to access information about their disease, including independent sources and ones recommended to them by the professional team treating them.
Half (51%) of respondents said they kept in contact through digital means with other patients they had met during treatment. Twelve percent contacted others or started new digital relationships with people they had never met in person.
However, most of the patients were still most likely to get information about their treatment from professionals in a face-to-face environment, such as when visiting their doctor.
“This is a reassuring and appropriate finding, as this is the conventional means by which teenage and young adult oncology care is delivered by the multidisciplinary team, whether the young people choose to engage or not,” Abrol said.
At the same time, many survey respondents expressed a desire for virtual online groups (54.3%), online counseling or psychological support (43.5%), and the ability to receive (66.3%) and share (48.9%) clinical information online.
Young adults (ages 19 to 24) were more interested than adolescents (ages 13 to 18) in online counseling options and preferred receiving clinical information online.
The researchers said this may reflect young adults’ greater independence, resilience, breadth of experience in the digital world, and confidence in discussing clinical matters online.
Abrol believes these preliminary results can help inform the development of local, national, and global services to teenagers and young adults with cancer to address their unmet needs.
“These digital support resources have the potential to improve patient experience and engagement for an important subsection of teenagers and young people treated for cancer,” Abrol said.
A recent survey of young cancer patients in the UK revealed their desire for additional digital oncology resources.
The survey showed that many of the patients already used digital resources to access information about their cancer.
However, many also expressed a need for additional resources such as online counseling or psychological support.
Esha Abrol, of Camden and Islington NHS Foundation Trust in London, UK, and her colleagues reported these findings in the Journal of Cancer Survivorship.
The researchers surveyed 102 cancer patients, ages 13 to 24, about digital media use.
The patients reported having active digital lives, with 41.6% of them rating digital resources as “essential” to their lives.
The patients reported using a variety of healthcare-related digital resources to access information about their disease, including independent sources and ones recommended to them by the professional team treating them.
Half (51%) of respondents said they kept in contact through digital means with other patients they had met during treatment. Twelve percent contacted others or started new digital relationships with people they had never met in person.
However, most of the patients were still most likely to get information about their treatment from professionals in a face-to-face environment, such as when visiting their doctor.
“This is a reassuring and appropriate finding, as this is the conventional means by which teenage and young adult oncology care is delivered by the multidisciplinary team, whether the young people choose to engage or not,” Abrol said.
At the same time, many survey respondents expressed a desire for virtual online groups (54.3%), online counseling or psychological support (43.5%), and the ability to receive (66.3%) and share (48.9%) clinical information online.
Young adults (ages 19 to 24) were more interested than adolescents (ages 13 to 18) in online counseling options and preferred receiving clinical information online.
The researchers said this may reflect young adults’ greater independence, resilience, breadth of experience in the digital world, and confidence in discussing clinical matters online.
Abrol believes these preliminary results can help inform the development of local, national, and global services to teenagers and young adults with cancer to address their unmet needs.
“These digital support resources have the potential to improve patient experience and engagement for an important subsection of teenagers and young people treated for cancer,” Abrol said.
FDA alert: pembrolizumab ups mortality risk in multiple myeloma
The use of pembrolizumab (Keytruda) in combination with dexamethasone and either lenalidomide or pomalidomide is associated with an increased risk of death in patients with multiple myeloma, according to an alert from the Food and Drug Administration.
The FDA issued the alert on Aug. 31 to inform the public, health care professionals, and oncology clinical investigators of the risk, which became apparent during the course of two now-halted clinical trials.
Among 249 patients in KEYNOTE-183, which evaluated pomalidomide and low-dose dexamethasone with or without pembrolizumab in patients with relapsed and refractory multiple myeloma who had received at least two prior lines of therapy, the relative risk of death was increased more than 50% among those in the pembrolizumab-containing investigational arm, compared with the control arm (hazard ratio, 1.61).
Among 301 patients in KEYNOTE-185, which evaluated lenalidomide and low-dose dexamethasone with or without pembrolizumab in patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant, the relative risk of death was nearly doubled in the pembrolizumab-containing investigational arm, compared with the control arm (hazard ratio, 2.06).
“On July 3, 2017, the FDA required that all patients in these trials be discontinued from further investigation with this drug, because interim results from both trials demonstrated an increased risk of death for patients receiving Keytruda when it was combined with an immunomodulatory agent as compared to the control group,” according to the statement. “Merck & Co., Inc. [the maker of Keytruda] was made aware of the issue through an external data monitoring committee recommendation and suspended the trials to enrollment on June 12, 2017.”
The FDA statement and actions by Merck do not apply to patients using the drug for approved indications, which include melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability–high (MSI-H) cancer.
“Patients on Keytruda for an approved use should continue to take their medication as directed by their health care professional,” according to the FDA, which noted in its statement that the agency will be working directly with sponsors and investigators of other ongoing trials of the drug and other PD-1/PD-L1 cancer drugs to “determine the extent of safety issues.”
In a separate statement, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research further stressed that the FDA is “actively examining the data from the Keytruda trials and working directly with Merck to better understand the true cause of the safety concerns.”
“The FDA will take appropriate action as warranted to ensure patients enrolled in these trials are protected and that doctors and clinical trial researchers understand the risks associated with this investigational use. We are communicating now, given the serious nature of the safety issue, to remind doctors and patients that Keytruda is not approved for the treatment of multiple myeloma and should not be given to patients in combination with any immunomodulatory agents, including Revlimid (lenalidomide) and Pomalyst (pomalidomide), for the treatment of multiple myeloma,” she said.
Health care professionals and consumers are encouraged to report adverse events and side effects related to Keytruda or similar product to FDA’s MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch/report, or by calling 800-332-1088 to request a reporting form.
sworcester@frontlinemedcom.com
The use of pembrolizumab (Keytruda) in combination with dexamethasone and either lenalidomide or pomalidomide is associated with an increased risk of death in patients with multiple myeloma, according to an alert from the Food and Drug Administration.
The FDA issued the alert on Aug. 31 to inform the public, health care professionals, and oncology clinical investigators of the risk, which became apparent during the course of two now-halted clinical trials.
Among 249 patients in KEYNOTE-183, which evaluated pomalidomide and low-dose dexamethasone with or without pembrolizumab in patients with relapsed and refractory multiple myeloma who had received at least two prior lines of therapy, the relative risk of death was increased more than 50% among those in the pembrolizumab-containing investigational arm, compared with the control arm (hazard ratio, 1.61).
Among 301 patients in KEYNOTE-185, which evaluated lenalidomide and low-dose dexamethasone with or without pembrolizumab in patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant, the relative risk of death was nearly doubled in the pembrolizumab-containing investigational arm, compared with the control arm (hazard ratio, 2.06).
“On July 3, 2017, the FDA required that all patients in these trials be discontinued from further investigation with this drug, because interim results from both trials demonstrated an increased risk of death for patients receiving Keytruda when it was combined with an immunomodulatory agent as compared to the control group,” according to the statement. “Merck & Co., Inc. [the maker of Keytruda] was made aware of the issue through an external data monitoring committee recommendation and suspended the trials to enrollment on June 12, 2017.”
The FDA statement and actions by Merck do not apply to patients using the drug for approved indications, which include melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability–high (MSI-H) cancer.
“Patients on Keytruda for an approved use should continue to take their medication as directed by their health care professional,” according to the FDA, which noted in its statement that the agency will be working directly with sponsors and investigators of other ongoing trials of the drug and other PD-1/PD-L1 cancer drugs to “determine the extent of safety issues.”
In a separate statement, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research further stressed that the FDA is “actively examining the data from the Keytruda trials and working directly with Merck to better understand the true cause of the safety concerns.”
“The FDA will take appropriate action as warranted to ensure patients enrolled in these trials are protected and that doctors and clinical trial researchers understand the risks associated with this investigational use. We are communicating now, given the serious nature of the safety issue, to remind doctors and patients that Keytruda is not approved for the treatment of multiple myeloma and should not be given to patients in combination with any immunomodulatory agents, including Revlimid (lenalidomide) and Pomalyst (pomalidomide), for the treatment of multiple myeloma,” she said.
Health care professionals and consumers are encouraged to report adverse events and side effects related to Keytruda or similar product to FDA’s MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch/report, or by calling 800-332-1088 to request a reporting form.
sworcester@frontlinemedcom.com
The use of pembrolizumab (Keytruda) in combination with dexamethasone and either lenalidomide or pomalidomide is associated with an increased risk of death in patients with multiple myeloma, according to an alert from the Food and Drug Administration.
The FDA issued the alert on Aug. 31 to inform the public, health care professionals, and oncology clinical investigators of the risk, which became apparent during the course of two now-halted clinical trials.
Among 249 patients in KEYNOTE-183, which evaluated pomalidomide and low-dose dexamethasone with or without pembrolizumab in patients with relapsed and refractory multiple myeloma who had received at least two prior lines of therapy, the relative risk of death was increased more than 50% among those in the pembrolizumab-containing investigational arm, compared with the control arm (hazard ratio, 1.61).
Among 301 patients in KEYNOTE-185, which evaluated lenalidomide and low-dose dexamethasone with or without pembrolizumab in patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant, the relative risk of death was nearly doubled in the pembrolizumab-containing investigational arm, compared with the control arm (hazard ratio, 2.06).
“On July 3, 2017, the FDA required that all patients in these trials be discontinued from further investigation with this drug, because interim results from both trials demonstrated an increased risk of death for patients receiving Keytruda when it was combined with an immunomodulatory agent as compared to the control group,” according to the statement. “Merck & Co., Inc. [the maker of Keytruda] was made aware of the issue through an external data monitoring committee recommendation and suspended the trials to enrollment on June 12, 2017.”
The FDA statement and actions by Merck do not apply to patients using the drug for approved indications, which include melanoma, lung cancer, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, and microsatellite instability–high (MSI-H) cancer.
“Patients on Keytruda for an approved use should continue to take their medication as directed by their health care professional,” according to the FDA, which noted in its statement that the agency will be working directly with sponsors and investigators of other ongoing trials of the drug and other PD-1/PD-L1 cancer drugs to “determine the extent of safety issues.”
In a separate statement, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research further stressed that the FDA is “actively examining the data from the Keytruda trials and working directly with Merck to better understand the true cause of the safety concerns.”
“The FDA will take appropriate action as warranted to ensure patients enrolled in these trials are protected and that doctors and clinical trial researchers understand the risks associated with this investigational use. We are communicating now, given the serious nature of the safety issue, to remind doctors and patients that Keytruda is not approved for the treatment of multiple myeloma and should not be given to patients in combination with any immunomodulatory agents, including Revlimid (lenalidomide) and Pomalyst (pomalidomide), for the treatment of multiple myeloma,” she said.
Health care professionals and consumers are encouraged to report adverse events and side effects related to Keytruda or similar product to FDA’s MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch/report, or by calling 800-332-1088 to request a reporting form.
sworcester@frontlinemedcom.com
CNS lymphoma responds to CAR T-cell therapy
Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.
The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).
When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.
While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.
“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.
“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”
Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.
The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.
The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.
One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.
The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.
While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.
“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”
Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.
The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).
When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.
While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.
“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.
“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”
Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.
The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.
The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.
One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.
The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.
While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.
“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”
Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.
The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).
When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.
While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.
“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.
“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”
Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.
The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.
The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.
One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.
The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.
While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.
“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”
FDA grants Priority Review to Gazyva for follicular lymphoma
Gazyva (obinutuzumab) has been granted a Priority Review by the Food and Drug Administration for the treatment of previously untreated follicular lymphoma, according to a press release from Genentech.
FDA approval was based on results from the GALLIUM study, a phase 3 trial comparing Gazyva to Rituxan (rituximab). Patients who received Gazyva plus chemotherapy followed by Gazyva therapy alone for 2 years had a 32% improvement in progression-free survival during the 41.1 month follow-up period, compared with the patient group who received Rituxan plus chemotherapy followed by 2 years of Rituxan therapy alone. Median progression-free survival has not been reached in either arm of the study.
The most common adverse events that occurred more often in the Gazyva arm of the study were low white blood cell count, infections, infusion-related reactions, low platelet count, new tumors, and cardiac events.
“Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible,” Dr. Sandra Horning, chief medical officer and head of Genentech’s Global Product Development said in the press release.
The FDA is expected to make a decision on approval under Priority Review by Dec. 23, 2017.
Find the full press release on the Genentech website.
Gazyva (obinutuzumab) has been granted a Priority Review by the Food and Drug Administration for the treatment of previously untreated follicular lymphoma, according to a press release from Genentech.
FDA approval was based on results from the GALLIUM study, a phase 3 trial comparing Gazyva to Rituxan (rituximab). Patients who received Gazyva plus chemotherapy followed by Gazyva therapy alone for 2 years had a 32% improvement in progression-free survival during the 41.1 month follow-up period, compared with the patient group who received Rituxan plus chemotherapy followed by 2 years of Rituxan therapy alone. Median progression-free survival has not been reached in either arm of the study.
The most common adverse events that occurred more often in the Gazyva arm of the study were low white blood cell count, infections, infusion-related reactions, low platelet count, new tumors, and cardiac events.
“Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible,” Dr. Sandra Horning, chief medical officer and head of Genentech’s Global Product Development said in the press release.
The FDA is expected to make a decision on approval under Priority Review by Dec. 23, 2017.
Find the full press release on the Genentech website.
Gazyva (obinutuzumab) has been granted a Priority Review by the Food and Drug Administration for the treatment of previously untreated follicular lymphoma, according to a press release from Genentech.
FDA approval was based on results from the GALLIUM study, a phase 3 trial comparing Gazyva to Rituxan (rituximab). Patients who received Gazyva plus chemotherapy followed by Gazyva therapy alone for 2 years had a 32% improvement in progression-free survival during the 41.1 month follow-up period, compared with the patient group who received Rituxan plus chemotherapy followed by 2 years of Rituxan therapy alone. Median progression-free survival has not been reached in either arm of the study.
The most common adverse events that occurred more often in the Gazyva arm of the study were low white blood cell count, infections, infusion-related reactions, low platelet count, new tumors, and cardiac events.
“Based on the GALLIUM study, Gazyva-based treatment significantly improved progression-free survival over the current standard of care, and we are committed to bringing this potential new option to patients as soon as possible,” Dr. Sandra Horning, chief medical officer and head of Genentech’s Global Product Development said in the press release.
The FDA is expected to make a decision on approval under Priority Review by Dec. 23, 2017.
Find the full press release on the Genentech website.