Hodgkin Lymphoma

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

COPENHAGEN – Nivolumab may be an effective salvage therapy option for adults with Hodgkin lymphoma whose disease has progressed despite transplant and treatment with brentuximab vedotin, investigators reported.

In a subcohort of patients from the Checkmate 205 phase II trial, 80 patients with Hodgkin lymphoma who had disease progression following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris), nivolumab (Opdivo) therapy was associated with a 53% objective response rate according to independent reviewers, reported Dr. Anas Younes, chief of the lymphoma service at Memorial Sloan Kettering Cancer Center, New York.

“The PD-1 checkpoint inhibitor nivolumab is an important new treatment to address unmet needs in patients with classical Hodgkin lymphoma with progressive disease and limited treatment options, especially after autologous transplant,” he said at a briefing at the annual congress of the European Hematology Association.

Objective response rates as determined by both investigators and independent reviewers were “impressive,” and had “encouraging durability,” he added. The median duration of response at time of data cutoff was 7.8 months, and the majority of patients had ongoing responses at the time of the analysis, Dr. Younes said.

Nivolumab was recently approved by the Food and Drug Administration for the treatment of classical Hodgkin lymphoma that has relapsed or progressed after ASCT followed by brentuximab vedotin.

In the Checkmate 205 registrational trial, 80 patients (median age 37, range 18-72 years) were assigned to receive nivolumab 3 mg/kg intravenously every 2 weeks. Patients were evaluated for response by both an independent radiologic review committee (IRRC) and investigators, using 2007 International Working Group response criteria. After a median follow-up of 8.9 months, the IRRC-rated objective response rate, the primary endpoint, was 66%, including 8.8% complete remissions (CR), and 57.5% partial remissions (PR).

Dr. Younes showed a waterfall plot indicating that nearly all patients had some degree of tumor regression, and all but one patient among the responders had tumor reductions of 50% or greater from baseline.

Among 43 patients who had had no response to brentuximab vedotin, subsequent treatment with nivolumab was associated with an IRRC-rated objective response rate of 72%. As noted, the median duration of response was 7.8 months, and the median time to response was 2.1 months.

As of the last follow-up, 33 of the 53 patients with IRRC-rated responses had retained response. The IRRC-determined 6-month progression-free survival rate was 77%, and the overall survival rate was 99%.

In all, 72 patients (90%) had a treatment-related adverse event. The most common events occurring in 15% or more of patients were fatigue, infusion-related reactions, and rash. Most of the immune-mediated adverse events were of low grade and manageable, and there were no treatment-related deaths, Dr. Younes said.

Briefing moderator Dr. Anton Hagenbeek, professor of hematology at the University of Amsterdam, who was not involved in the study, asked whether nivolumab can be considered as a bridge to other therapies in this population.

Dr. Younes said that the “natural progression of a single-agent therapy that has efficacy is to combine it with other active agents, or use maybe in the adjuvant or maintenance setting in certain circumstances.”

“I don’t expect single-agent nivolumab to cure our patients,” he added.

A similarly designed clinical trial, MK-3457-087/KEYNOTE-087, is exploring the use of pembrolizumab (Keytruda). This trial is ongoing but does not have published data as yet.

Checkmate 205 is sponsored by Bristol-Myers Squibb. Dr. Younes has served as a consultant/advisor, received honoraria and/or research funding from Gilead Sciences, Curis, Incyte, Janssen, Seattle Genetics, Novartis, Celgene, Millennium, and Sanofi. Dr. Hagenbeek reported no relevant disclosures.

Mother and infant
Photo credit: Vera Kratochvil

A single-center retrospective study of 39 pregnant women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy indicates that delaying treatment until the second trimester is “likely safe and results in acceptable” outcomes for both mother and child.

Investigators also found that deferring therapy until after delivery did not adversely affect maternal outcomes.

In order to clarify the sometimes conflicting reports regarding management of lymphoma during pregnancy, investigators at MD Anderson Cancer Center in Houston, Texas, undertook the study to determine whether administering standard chemotherapy during the second and third trimesters has acceptable maternal and fetal outcomes.

Michelle A. Fanale, MD, and colleagues published their findings in JAMA Oncology.

Patient characteristics

Investigators identified 31 women with HL and 8 with NHL who were diagnosed between 1991 and 2014 and had sufficient pregnancy and follow-up data.
 
The women were a median age of 28 years (range 19-38). The patients with NHL were significantly older, P=0.004.

Approximately 20% of patients had B symptoms. Most were stage II disease (72%), and 80% were ECOG performance status 0 or 1.

About two thirds of patients had hemoglobin levels less than 12 g/dL.

Most patients did not have extranodal nonbone-marrow disease (82%), although there was a significant difference between those with HL (90%) and NHL (50%), P=0.03.

One third of patients had bulky disease, and 88% were in their second or third trimesters at diagnosis.

Three women electively terminated their pregnancies at diagnosis. Of the 36 remaining patients, 24 (61%) began antenatal therapy and 12 (31%) postponed therapy until after delivery.

Four patients received radiation therapy above the diaphragm at a median dose of 40.4 Gy.

Obstetric outcomes

Antenatal therapy was not associated with increased incidence of preterm delivery. Of the 24 women who received treatment during pregnancy, 7 (29%) gave birth prematurely compared with 5 of the 12 women (42%) who postponed treatment until after delivery, P=0.73.

The investigators noted that the miscarriage rate was approximately 10%, which was higher than previous studies.

Four patients had miscarriages, 2 during the first trimester and 2 during the second. Both patients who had miscarriages in the first trimester had received lymphoma treatment during that time.

And one of the patients who had antenatal therapy during the second trimester and had a miscarriage was critically ill, which the investigators believed was a contributing factor.

The second woman who miscarried after therapy in the second trimester had conceived twins through in vitro fertilization and miscarried at 23 weeks after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) therapy had been initiated at gestational week 15.

Investigators had fetal outcomes available for 31 of 32 patients who did not terminate or have a miscarriage. And these 31 infants had no anomalies at birth.

The investigators said that although the follow-up time is relatively short, they observed no malformations in the newborns.

Treatment responses and survival

The overall response rate (OR) was 91.7% and the complete response (CR) rate was 75.0% for the 24 patients who started treatment during pregnancy.

And for those 12 women who deferred therapy until delivery, both ORR and CR rates were 91.7%.

The 5-year progression-free survival (PFS) and OS were 74.7% and 82.4%, respectively, for all women. The median follow-up was 67.9 months (range 8.8 to 277.5).

For the 31 women with HL, the 5-year PFS and OS were 69.9% and 80%, respectively.

And for the 8 women with NHL, the 5-year PFS and OS were 85.7% and 83.3%, respectively.

Investigators found no difference in PFS or OS (P=0.84) based on undergoing antenatal lymphoma treatment among the 36 women who did not terminate their pregnancies at diagnosis.

The investigators conducted a univariate analysis and found that for the 36 women who did not electively terminate their pregnancies, the following were associated with increased risk of disease progression:

•    Bulky disease—hazard ratio [HR] 3.6, P = 0.06
•    Extranodal nonbone marrow involvement—HR 4.2, P = 0.04
•    Poor ECOG performance status—HR 3.9, P = 0.005

Poor performance status was also associated with OS, HR 8.88, P = 0.004.

Multivariate analysis revealed significant associations in terms of OS and PFS for extranodal nonbone marrow involvement and performance status:

•    Nonbone marrow involvement—OS HR, 73.5, P = 0.02; PFS HR 8.26, P = 0.01
•    Performance status—OS HR, 26.7, P = 0.003; PFS HR, 4.89, P = 0.002

The investigators concluded that because they found no differences in PFS or OS according to whether patients received antenatal therapy, they believe that disease factors, rather than treatment-related factors, influence worse maternal outcomes.

They recommended delaying therapy until the second trimester if that can be accomplished without harm to the patient.

Mother and infant
Photo credit: Vera Kratochvil

A single-center retrospective study of 39 pregnant women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy indicates that delaying treatment until the second trimester is “likely safe and results in acceptable” outcomes for both mother and child.

Investigators also found that deferring therapy until after delivery did not adversely affect maternal outcomes.

In order to clarify the sometimes conflicting reports regarding management of lymphoma during pregnancy, investigators at MD Anderson Cancer Center in Houston, Texas, undertook the study to determine whether administering standard chemotherapy during the second and third trimesters has acceptable maternal and fetal outcomes.

Michelle A. Fanale, MD, and colleagues published their findings in JAMA Oncology.

Patient characteristics

Investigators identified 31 women with HL and 8 with NHL who were diagnosed between 1991 and 2014 and had sufficient pregnancy and follow-up data.
 
The women were a median age of 28 years (range 19-38). The patients with NHL were significantly older, P=0.004.

Approximately 20% of patients had B symptoms. Most were stage II disease (72%), and 80% were ECOG performance status 0 or 1.

About two thirds of patients had hemoglobin levels less than 12 g/dL.

Most patients did not have extranodal nonbone-marrow disease (82%), although there was a significant difference between those with HL (90%) and NHL (50%), P=0.03.

One third of patients had bulky disease, and 88% were in their second or third trimesters at diagnosis.

Three women electively terminated their pregnancies at diagnosis. Of the 36 remaining patients, 24 (61%) began antenatal therapy and 12 (31%) postponed therapy until after delivery.

Four patients received radiation therapy above the diaphragm at a median dose of 40.4 Gy.

Obstetric outcomes

Antenatal therapy was not associated with increased incidence of preterm delivery. Of the 24 women who received treatment during pregnancy, 7 (29%) gave birth prematurely compared with 5 of the 12 women (42%) who postponed treatment until after delivery, P=0.73.

The investigators noted that the miscarriage rate was approximately 10%, which was higher than previous studies.

Four patients had miscarriages, 2 during the first trimester and 2 during the second. Both patients who had miscarriages in the first trimester had received lymphoma treatment during that time.

And one of the patients who had antenatal therapy during the second trimester and had a miscarriage was critically ill, which the investigators believed was a contributing factor.

The second woman who miscarried after therapy in the second trimester had conceived twins through in vitro fertilization and miscarried at 23 weeks after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) therapy had been initiated at gestational week 15.

Investigators had fetal outcomes available for 31 of 32 patients who did not terminate or have a miscarriage. And these 31 infants had no anomalies at birth.

The investigators said that although the follow-up time is relatively short, they observed no malformations in the newborns.

Treatment responses and survival

The overall response rate (OR) was 91.7% and the complete response (CR) rate was 75.0% for the 24 patients who started treatment during pregnancy.

And for those 12 women who deferred therapy until delivery, both ORR and CR rates were 91.7%.

The 5-year progression-free survival (PFS) and OS were 74.7% and 82.4%, respectively, for all women. The median follow-up was 67.9 months (range 8.8 to 277.5).

For the 31 women with HL, the 5-year PFS and OS were 69.9% and 80%, respectively.

And for the 8 women with NHL, the 5-year PFS and OS were 85.7% and 83.3%, respectively.

Investigators found no difference in PFS or OS (P=0.84) based on undergoing antenatal lymphoma treatment among the 36 women who did not terminate their pregnancies at diagnosis.

The investigators conducted a univariate analysis and found that for the 36 women who did not electively terminate their pregnancies, the following were associated with increased risk of disease progression:

•    Bulky disease—hazard ratio [HR] 3.6, P = 0.06
•    Extranodal nonbone marrow involvement—HR 4.2, P = 0.04
•    Poor ECOG performance status—HR 3.9, P = 0.005

Poor performance status was also associated with OS, HR 8.88, P = 0.004.

Multivariate analysis revealed significant associations in terms of OS and PFS for extranodal nonbone marrow involvement and performance status:

•    Nonbone marrow involvement—OS HR, 73.5, P = 0.02; PFS HR 8.26, P = 0.01
•    Performance status—OS HR, 26.7, P = 0.003; PFS HR, 4.89, P = 0.002

The investigators concluded that because they found no differences in PFS or OS according to whether patients received antenatal therapy, they believe that disease factors, rather than treatment-related factors, influence worse maternal outcomes.

They recommended delaying therapy until the second trimester if that can be accomplished without harm to the patient.

Mother and infant
Photo credit: Vera Kratochvil

A single-center retrospective study of 39 pregnant women diagnosed with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) during pregnancy indicates that delaying treatment until the second trimester is “likely safe and results in acceptable” outcomes for both mother and child.

Investigators also found that deferring therapy until after delivery did not adversely affect maternal outcomes.

In order to clarify the sometimes conflicting reports regarding management of lymphoma during pregnancy, investigators at MD Anderson Cancer Center in Houston, Texas, undertook the study to determine whether administering standard chemotherapy during the second and third trimesters has acceptable maternal and fetal outcomes.

Michelle A. Fanale, MD, and colleagues published their findings in JAMA Oncology.

Patient characteristics

Investigators identified 31 women with HL and 8 with NHL who were diagnosed between 1991 and 2014 and had sufficient pregnancy and follow-up data.
 
The women were a median age of 28 years (range 19-38). The patients with NHL were significantly older, P=0.004.

Approximately 20% of patients had B symptoms. Most were stage II disease (72%), and 80% were ECOG performance status 0 or 1.

About two thirds of patients had hemoglobin levels less than 12 g/dL.

Most patients did not have extranodal nonbone-marrow disease (82%), although there was a significant difference between those with HL (90%) and NHL (50%), P=0.03.

One third of patients had bulky disease, and 88% were in their second or third trimesters at diagnosis.

Three women electively terminated their pregnancies at diagnosis. Of the 36 remaining patients, 24 (61%) began antenatal therapy and 12 (31%) postponed therapy until after delivery.

Four patients received radiation therapy above the diaphragm at a median dose of 40.4 Gy.

Obstetric outcomes

Antenatal therapy was not associated with increased incidence of preterm delivery. Of the 24 women who received treatment during pregnancy, 7 (29%) gave birth prematurely compared with 5 of the 12 women (42%) who postponed treatment until after delivery, P=0.73.

The investigators noted that the miscarriage rate was approximately 10%, which was higher than previous studies.

Four patients had miscarriages, 2 during the first trimester and 2 during the second. Both patients who had miscarriages in the first trimester had received lymphoma treatment during that time.

And one of the patients who had antenatal therapy during the second trimester and had a miscarriage was critically ill, which the investigators believed was a contributing factor.

The second woman who miscarried after therapy in the second trimester had conceived twins through in vitro fertilization and miscarried at 23 weeks after ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) therapy had been initiated at gestational week 15.

Investigators had fetal outcomes available for 31 of 32 patients who did not terminate or have a miscarriage. And these 31 infants had no anomalies at birth.

The investigators said that although the follow-up time is relatively short, they observed no malformations in the newborns.

Treatment responses and survival

The overall response rate (OR) was 91.7% and the complete response (CR) rate was 75.0% for the 24 patients who started treatment during pregnancy.

And for those 12 women who deferred therapy until delivery, both ORR and CR rates were 91.7%.

The 5-year progression-free survival (PFS) and OS were 74.7% and 82.4%, respectively, for all women. The median follow-up was 67.9 months (range 8.8 to 277.5).

For the 31 women with HL, the 5-year PFS and OS were 69.9% and 80%, respectively.

And for the 8 women with NHL, the 5-year PFS and OS were 85.7% and 83.3%, respectively.

Investigators found no difference in PFS or OS (P=0.84) based on undergoing antenatal lymphoma treatment among the 36 women who did not terminate their pregnancies at diagnosis.

The investigators conducted a univariate analysis and found that for the 36 women who did not electively terminate their pregnancies, the following were associated with increased risk of disease progression:

•    Bulky disease—hazard ratio [HR] 3.6, P = 0.06
•    Extranodal nonbone marrow involvement—HR 4.2, P = 0.04
•    Poor ECOG performance status—HR 3.9, P = 0.005

Poor performance status was also associated with OS, HR 8.88, P = 0.004.

Multivariate analysis revealed significant associations in terms of OS and PFS for extranodal nonbone marrow involvement and performance status:

•    Nonbone marrow involvement—OS HR, 73.5, P = 0.02; PFS HR 8.26, P = 0.01
•    Performance status—OS HR, 26.7, P = 0.003; PFS HR, 4.89, P = 0.002

The investigators concluded that because they found no differences in PFS or OS according to whether patients received antenatal therapy, they believe that disease factors, rather than treatment-related factors, influence worse maternal outcomes.

They recommended delaying therapy until the second trimester if that can be accomplished without harm to the patient.

CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.

After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.

The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.

In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.

Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.

According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.

Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.

[email protected]

On Twitter @maryjodales

CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.

After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.

The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.

In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.

Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.

According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.

Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.

[email protected]

On Twitter @maryjodales

CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.

After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.

The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.

In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.

Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.

According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.

Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.

[email protected]

On Twitter @maryjodales

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Adolescents and young adults (AYAs) are less likely than children to survive 8 relatively common types of cancer, according to a long-running study of cancer survival across Europe.

The study showed that AYAs had significantly worse survival rates than children if they were diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin or non-Hodgkin lymphoma (NHL), and 4 types of solid tumor malignancies.

The study’s authors say that variations in survival between age groups are due to a number of factors, including delays in diagnosis and treatment, a lack of treatment guidelines and clinical trials specifically for AYAs, and differences in the biology of some cancers.

“The good news is that the number of children, adolescents, and young adults surviving for at least 5 years after diagnosis has risen steadily over time in Europe,” said author Annalisa Trama, PhD, of The National Institute of Cancer (Istituto Nazionale dei Tumori: Fondazione IRCCS) in Milan, Italy.

“Across all cancers, the level of improvement is similar in these age groups. This contrasts with earlier results that adolescents and young adults diagnosed up to the 1990s were lagging behind children in terms of survival.”

“However, we found that adolescents and young adults still tend to die earlier than children for several cancers common to these age groups, particularly blood cancers like leukemias and non-Hodgkin’s lymphoma.”

Dr Trama and her colleagues reported these findings in The Lancet Oncology.

The researchers compared survival between AYAs (ages 15 to 39), children (ages 0 to 14), and adults (ages 40 to 69) who were diagnosed from 2000 to 2007 and followed up to at least 2008.

The team analyzed data from population-based cancer registries covering all or part of 27 European countries* and estimated 5-year survival for 56,505 cancer cases in children; 312,483 in AYAs; and 3,567,383 in adults. The researchers also analyzed changes in survival over time from 1999 to 2007.

For AYAs, survival at 5 years from diagnosis for all cancers combined was 82% for 2005-2007, which is up from 79% for 1999-2001 (P<0.0001). In children, survival improved from 76% to 79% over the same time period (P<0.0001).

Survival improved significantly in children and AYAs for ALL (P<0.0001) and NHL (P<0.0001 in AYAs and P=0.023 in children). On the other hand, between 1999 and 2007, survival rates remained unchanged for AYAs with AML (around 50%).

Overall, AYAs had slightly better 5-year survival than children because they were diagnosed more often with cancers with fairly good prognoses—Hodgkin lymphoma, NHL, germ cell tumors, melanoma, thyroid cancer, and breast cancer.

However, the overall survival rates conceal differences between specific cancers. Survival was significantly worse for AYAs than for children when it came to 8 relatively common cancers affecting both age groups:

• ALL—55.6% for AYAs and 85.8% for children (P<0.0001)
• AML—49.8% and 60.5%, respectively (P<0.0001)
• Hodgkin lymphoma—92.9% and 95.1%, respectively (P<0.0001)
• NHL—77.4% and 83.0%, respectively (P<0.0001)
• Astrocytomas—46.4% and 61.9%, respectively (P<0.0001)
• Ewing’s sarcoma of bone—49.3% and 66.6%, respectively (P<0.0001)
• Rhabdomyosarcoma—37.8% and 66.6%, respectively (P<0.0001)
• Osteosarcoma—61.5% and 66.8%, respectively (P=0.011).

AYAs had a survival advantage over adults for almost all major cancers affecting both age groups, supporting the idea that younger patients with few other illnesses are likely to fare better than older patients.

There are only 2 types of cancer for which AYAs were at a survival disadvantage—breast (83.5% vs 87.0%) and prostate (79.9% vs 89.8%).

Dr Trama and her colleagues pointed out that this analysis pre-dates recent initiatives to improve outcomes for AYAs that have been implemented in several European countries.

“The European Network for Teenagers and Young Adults with Cancer is advocating collaboration between pediatric and adult oncologists, greater access to clinical trials and research to improve treatments for this specific age group, as well as developing adolescent and young adult-specific practice guidelines, encouraging healthier lifestyles and the greater involvement of patients and patients support groups,” Dr Trama said.

“This study will provide an important starting point from which to evaluate whether these initiatives will reduce the gulf in survival between European adolescents and young adults and children with cancer.”

*Finland, Iceland, Norway, Sweden, England, Ireland, Northern Ireland, Scotland, Wales, Austria, Belgium, France, Germany, Netherlands, Switzerland, Croatia, Italy, Malta, Portugal, Slovenia, Spain, Bulgaria, Estonia, Latvia, Lithuania, Poland, and Slovakia

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Adolescents and young adults (AYAs) are less likely than children to survive 8 relatively common types of cancer, according to a long-running study of cancer survival across Europe.

The study showed that AYAs had significantly worse survival rates than children if they were diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin or non-Hodgkin lymphoma (NHL), and 4 types of solid tumor malignancies.

The study’s authors say that variations in survival between age groups are due to a number of factors, including delays in diagnosis and treatment, a lack of treatment guidelines and clinical trials specifically for AYAs, and differences in the biology of some cancers.

“The good news is that the number of children, adolescents, and young adults surviving for at least 5 years after diagnosis has risen steadily over time in Europe,” said author Annalisa Trama, PhD, of The National Institute of Cancer (Istituto Nazionale dei Tumori: Fondazione IRCCS) in Milan, Italy.

“Across all cancers, the level of improvement is similar in these age groups. This contrasts with earlier results that adolescents and young adults diagnosed up to the 1990s were lagging behind children in terms of survival.”

“However, we found that adolescents and young adults still tend to die earlier than children for several cancers common to these age groups, particularly blood cancers like leukemias and non-Hodgkin’s lymphoma.”

Dr Trama and her colleagues reported these findings in The Lancet Oncology.

The researchers compared survival between AYAs (ages 15 to 39), children (ages 0 to 14), and adults (ages 40 to 69) who were diagnosed from 2000 to 2007 and followed up to at least 2008.

The team analyzed data from population-based cancer registries covering all or part of 27 European countries* and estimated 5-year survival for 56,505 cancer cases in children; 312,483 in AYAs; and 3,567,383 in adults. The researchers also analyzed changes in survival over time from 1999 to 2007.

For AYAs, survival at 5 years from diagnosis for all cancers combined was 82% for 2005-2007, which is up from 79% for 1999-2001 (P<0.0001). In children, survival improved from 76% to 79% over the same time period (P<0.0001).

Survival improved significantly in children and AYAs for ALL (P<0.0001) and NHL (P<0.0001 in AYAs and P=0.023 in children). On the other hand, between 1999 and 2007, survival rates remained unchanged for AYAs with AML (around 50%).

Overall, AYAs had slightly better 5-year survival than children because they were diagnosed more often with cancers with fairly good prognoses—Hodgkin lymphoma, NHL, germ cell tumors, melanoma, thyroid cancer, and breast cancer.

However, the overall survival rates conceal differences between specific cancers. Survival was significantly worse for AYAs than for children when it came to 8 relatively common cancers affecting both age groups:

• ALL—55.6% for AYAs and 85.8% for children (P<0.0001)
• AML—49.8% and 60.5%, respectively (P<0.0001)
• Hodgkin lymphoma—92.9% and 95.1%, respectively (P<0.0001)
• NHL—77.4% and 83.0%, respectively (P<0.0001)
• Astrocytomas—46.4% and 61.9%, respectively (P<0.0001)
• Ewing’s sarcoma of bone—49.3% and 66.6%, respectively (P<0.0001)
• Rhabdomyosarcoma—37.8% and 66.6%, respectively (P<0.0001)
• Osteosarcoma—61.5% and 66.8%, respectively (P=0.011).

AYAs had a survival advantage over adults for almost all major cancers affecting both age groups, supporting the idea that younger patients with few other illnesses are likely to fare better than older patients.

There are only 2 types of cancer for which AYAs were at a survival disadvantage—breast (83.5% vs 87.0%) and prostate (79.9% vs 89.8%).

Dr Trama and her colleagues pointed out that this analysis pre-dates recent initiatives to improve outcomes for AYAs that have been implemented in several European countries.

“The European Network for Teenagers and Young Adults with Cancer is advocating collaboration between pediatric and adult oncologists, greater access to clinical trials and research to improve treatments for this specific age group, as well as developing adolescent and young adult-specific practice guidelines, encouraging healthier lifestyles and the greater involvement of patients and patients support groups,” Dr Trama said.

“This study will provide an important starting point from which to evaluate whether these initiatives will reduce the gulf in survival between European adolescents and young adults and children with cancer.”

*Finland, Iceland, Norway, Sweden, England, Ireland, Northern Ireland, Scotland, Wales, Austria, Belgium, France, Germany, Netherlands, Switzerland, Croatia, Italy, Malta, Portugal, Slovenia, Spain, Bulgaria, Estonia, Latvia, Lithuania, Poland, and Slovakia

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Adolescents and young adults (AYAs) are less likely than children to survive 8 relatively common types of cancer, according to a long-running study of cancer survival across Europe.

The study showed that AYAs had significantly worse survival rates than children if they were diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin or non-Hodgkin lymphoma (NHL), and 4 types of solid tumor malignancies.

The study’s authors say that variations in survival between age groups are due to a number of factors, including delays in diagnosis and treatment, a lack of treatment guidelines and clinical trials specifically for AYAs, and differences in the biology of some cancers.

“The good news is that the number of children, adolescents, and young adults surviving for at least 5 years after diagnosis has risen steadily over time in Europe,” said author Annalisa Trama, PhD, of The National Institute of Cancer (Istituto Nazionale dei Tumori: Fondazione IRCCS) in Milan, Italy.

“Across all cancers, the level of improvement is similar in these age groups. This contrasts with earlier results that adolescents and young adults diagnosed up to the 1990s were lagging behind children in terms of survival.”

“However, we found that adolescents and young adults still tend to die earlier than children for several cancers common to these age groups, particularly blood cancers like leukemias and non-Hodgkin’s lymphoma.”

Dr Trama and her colleagues reported these findings in The Lancet Oncology.

The researchers compared survival between AYAs (ages 15 to 39), children (ages 0 to 14), and adults (ages 40 to 69) who were diagnosed from 2000 to 2007 and followed up to at least 2008.

The team analyzed data from population-based cancer registries covering all or part of 27 European countries* and estimated 5-year survival for 56,505 cancer cases in children; 312,483 in AYAs; and 3,567,383 in adults. The researchers also analyzed changes in survival over time from 1999 to 2007.

For AYAs, survival at 5 years from diagnosis for all cancers combined was 82% for 2005-2007, which is up from 79% for 1999-2001 (P<0.0001). In children, survival improved from 76% to 79% over the same time period (P<0.0001).

Survival improved significantly in children and AYAs for ALL (P<0.0001) and NHL (P<0.0001 in AYAs and P=0.023 in children). On the other hand, between 1999 and 2007, survival rates remained unchanged for AYAs with AML (around 50%).

Overall, AYAs had slightly better 5-year survival than children because they were diagnosed more often with cancers with fairly good prognoses—Hodgkin lymphoma, NHL, germ cell tumors, melanoma, thyroid cancer, and breast cancer.

However, the overall survival rates conceal differences between specific cancers. Survival was significantly worse for AYAs than for children when it came to 8 relatively common cancers affecting both age groups:

• ALL—55.6% for AYAs and 85.8% for children (P<0.0001)
• AML—49.8% and 60.5%, respectively (P<0.0001)
• Hodgkin lymphoma—92.9% and 95.1%, respectively (P<0.0001)
• NHL—77.4% and 83.0%, respectively (P<0.0001)
• Astrocytomas—46.4% and 61.9%, respectively (P<0.0001)
• Ewing’s sarcoma of bone—49.3% and 66.6%, respectively (P<0.0001)
• Rhabdomyosarcoma—37.8% and 66.6%, respectively (P<0.0001)
• Osteosarcoma—61.5% and 66.8%, respectively (P=0.011).

AYAs had a survival advantage over adults for almost all major cancers affecting both age groups, supporting the idea that younger patients with few other illnesses are likely to fare better than older patients.

There are only 2 types of cancer for which AYAs were at a survival disadvantage—breast (83.5% vs 87.0%) and prostate (79.9% vs 89.8%).

Dr Trama and her colleagues pointed out that this analysis pre-dates recent initiatives to improve outcomes for AYAs that have been implemented in several European countries.

“The European Network for Teenagers and Young Adults with Cancer is advocating collaboration between pediatric and adult oncologists, greater access to clinical trials and research to improve treatments for this specific age group, as well as developing adolescent and young adult-specific practice guidelines, encouraging healthier lifestyles and the greater involvement of patients and patients support groups,” Dr Trama said.

“This study will provide an important starting point from which to evaluate whether these initiatives will reduce the gulf in survival between European adolescents and young adults and children with cancer.”

*Finland, Iceland, Norway, Sweden, England, Ireland, Northern Ireland, Scotland, Wales, Austria, Belgium, France, Germany, Netherlands, Switzerland, Croatia, Italy, Malta, Portugal, Slovenia, Spain, Bulgaria, Estonia, Latvia, Lithuania, Poland, and Slovakia

Brentuximab vedotin

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended extending the current conditional approval of brentuximab vedotin (Adcetris) to include the treatment of adults with CD30+ Hodgkin lymphoma (HL) at increased risk of relapse or progression following autologous stem cell transplant (ASCT).

The CHMP’s recommendation will now be reviewed by the European Commission (EC).

If the recommendation is formally adopted by the EC, brentuximab vedotin will be approved for the aforementioned indication in the 28 member states of the European Union as well as Norway, Liechtenstein, and Iceland.

Brentuximab vedotin already has conditional marketing authorization from the EC for 2 indications:

• To treat adults with relapsed or refractory CD30+ HL after ASCT or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• To treat adults with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL).

In January 2016, the EC approved a Type II variation to include data on the retreatment of adult patients with HL or sALCL who previously responded to brentuximab vedotin and later relapsed.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

AETHERA trial

The CHMP’s recommendation to extend the approval of brentuximab vedotin is based on results from the phase 3 AETHERA trial.

The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015 and presented at the 2014 ASH Annual Meeting.

The study enrolled 329 HL patients at risk of relapse or progression, including 165 on the brentuximab vedotin arm and 164 on the placebo arm.

Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.

Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.

The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).

The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).

In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).

Brentuximab vedotin

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended extending the current conditional approval of brentuximab vedotin (Adcetris) to include the treatment of adults with CD30+ Hodgkin lymphoma (HL) at increased risk of relapse or progression following autologous stem cell transplant (ASCT).

The CHMP’s recommendation will now be reviewed by the European Commission (EC).

If the recommendation is formally adopted by the EC, brentuximab vedotin will be approved for the aforementioned indication in the 28 member states of the European Union as well as Norway, Liechtenstein, and Iceland.

Brentuximab vedotin already has conditional marketing authorization from the EC for 2 indications:

• To treat adults with relapsed or refractory CD30+ HL after ASCT or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• To treat adults with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL).

In January 2016, the EC approved a Type II variation to include data on the retreatment of adult patients with HL or sALCL who previously responded to brentuximab vedotin and later relapsed.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

AETHERA trial

The CHMP’s recommendation to extend the approval of brentuximab vedotin is based on results from the phase 3 AETHERA trial.

The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015 and presented at the 2014 ASH Annual Meeting.

The study enrolled 329 HL patients at risk of relapse or progression, including 165 on the brentuximab vedotin arm and 164 on the placebo arm.

Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.

Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.

The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).

The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).

In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).

Brentuximab vedotin

Photo from Business Wire

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended extending the current conditional approval of brentuximab vedotin (Adcetris) to include the treatment of adults with CD30+ Hodgkin lymphoma (HL) at increased risk of relapse or progression following autologous stem cell transplant (ASCT).

The CHMP’s recommendation will now be reviewed by the European Commission (EC).

If the recommendation is formally adopted by the EC, brentuximab vedotin will be approved for the aforementioned indication in the 28 member states of the European Union as well as Norway, Liechtenstein, and Iceland.

Brentuximab vedotin already has conditional marketing authorization from the EC for 2 indications:

• To treat adults with relapsed or refractory CD30+ HL after ASCT or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
• To treat adults with relapsed or refractory systemic anaplastic large-cell lymphoma (sALCL).

In January 2016, the EC approved a Type II variation to include data on the retreatment of adult patients with HL or sALCL who previously responded to brentuximab vedotin and later relapsed.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

AETHERA trial

The CHMP’s recommendation to extend the approval of brentuximab vedotin is based on results from the phase 3 AETHERA trial.

The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following ASCT. Results from the trial were published in The Lancet in March 2015 and presented at the 2014 ASH Annual Meeting.

The study enrolled 329 HL patients at risk of relapse or progression, including 165 on the brentuximab vedotin arm and 164 on the placebo arm.

Patients were eligible for enrollment if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-ASCT relapse.

Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for those who received placebo.

The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).

The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).

In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).

HIV budding from a

cultured lymphocyte

Image courtesy of the CDC

A new study suggests that cancer patients with HIV are less likely to receive cancer treatment, regardless of insurance status and comorbidities.

Patients with HIV were less likely than their HIV-free peers to receive treatment for Hodgkin lymphoma, diffuse large B-cell lymphoma, and 7 solid tumor malignancies.

Gita Suneja, MD, of the University of Utah in Salt Lake City, and her colleagues reported these findings in Cancer.

The team used the National Cancer Data Base to study non-elderly US adults diagnosed with 10 common cancers from 2003 to 2011. There were a total of 10,265 HIV-infected patients and 2,219,232 HIV-free patients.

The researchers examined associations between HIV status and lack of cancer treatment, taking into account insurance status and comorbidities.

The results showed a lack of treatment among HIV patients for all of the cancers studied except anal cancer (relative risk [RR]=1.20, P=0.333).

So HIV-infected patients were more likely to lack cancer treatment for:

• Hodgkin lymphoma (RR=1.92, P<0.001)
• Diffuse large B-cell lymphoma (RR=1.82, P<0.001)
• Head and neck cancer (RR=1.48, P=0.013)
• Upper gastrointestinal tract cancer (RR=2.62, P<0.001)
• Colorectal cancer (RR=1.70, P=0.006)
• Lung cancer (RR=2.46, P<0.001)
• Breast cancer (RR=2.14, P=0.015)
• Cervical cancer (RR=2.81, P<0.001)
• Prostate cancer (RR=2.16, P<0.001).

The researchers said factors that predicted a lack of cancer treatment among HIV-infected individuals varied between those with solid tumors and those with lymphomas.

Advanced stage at the time of cancer diagnosis (stage IV vs stage I) meant HIV patients with solid tumors were less likely to receive cancer treatment, but lymphoma patients were more likely to receive cancer treatment.

Having a higher modified Charlson-Deyo comorbidity score (1 or 2+ vs 0) predicted a lack of cancer treatment for HIV-infected patients with lymphoma but not those with solid tumors.

And older age (45-64 vs 18-44) was associated with a lack of treatment for HIV-infected patients regardless of cancer type, but this was only significant for lymphoma patients.

For the entire cohort, black race (vs white) and a lack of private insurance (Medicaid, Medicare, uninsured, or unknown insurance status) were significant predictors for a lack of cancer treatment among HIV patients.

Still, the researchers noted that, even among privately insured patients, HIV-infected individuals were less likely to receive cancer treatment.

Dr Suneja and her colleagues said several factors may contribute to these findings. For one, HIV-infected patients have historically been excluded from cancer clinical trials, thereby limiting the applicability of trial results for this population.

In addition, cancer treatment guidelines specific to HIV-infected patients are not available for most cancer types. And clinicians may lack experience treating HIV-infected patients with cancer.

Furthermore, the psychosocial and economic challenges associated with the dual management of cancer and HIV treatment may make adherence to treatment a challenge.

HIV budding from a

cultured lymphocyte

Image courtesy of the CDC

A new study suggests that cancer patients with HIV are less likely to receive cancer treatment, regardless of insurance status and comorbidities.

Patients with HIV were less likely than their HIV-free peers to receive treatment for Hodgkin lymphoma, diffuse large B-cell lymphoma, and 7 solid tumor malignancies.

Gita Suneja, MD, of the University of Utah in Salt Lake City, and her colleagues reported these findings in Cancer.

The team used the National Cancer Data Base to study non-elderly US adults diagnosed with 10 common cancers from 2003 to 2011. There were a total of 10,265 HIV-infected patients and 2,219,232 HIV-free patients.

The researchers examined associations between HIV status and lack of cancer treatment, taking into account insurance status and comorbidities.

The results showed a lack of treatment among HIV patients for all of the cancers studied except anal cancer (relative risk [RR]=1.20, P=0.333).

So HIV-infected patients were more likely to lack cancer treatment for:

• Hodgkin lymphoma (RR=1.92, P<0.001)
• Diffuse large B-cell lymphoma (RR=1.82, P<0.001)
• Head and neck cancer (RR=1.48, P=0.013)
• Upper gastrointestinal tract cancer (RR=2.62, P<0.001)
• Colorectal cancer (RR=1.70, P=0.006)
• Lung cancer (RR=2.46, P<0.001)
• Breast cancer (RR=2.14, P=0.015)
• Cervical cancer (RR=2.81, P<0.001)
• Prostate cancer (RR=2.16, P<0.001).

The researchers said factors that predicted a lack of cancer treatment among HIV-infected individuals varied between those with solid tumors and those with lymphomas.

Advanced stage at the time of cancer diagnosis (stage IV vs stage I) meant HIV patients with solid tumors were less likely to receive cancer treatment, but lymphoma patients were more likely to receive cancer treatment.

Having a higher modified Charlson-Deyo comorbidity score (1 or 2+ vs 0) predicted a lack of cancer treatment for HIV-infected patients with lymphoma but not those with solid tumors.

And older age (45-64 vs 18-44) was associated with a lack of treatment for HIV-infected patients regardless of cancer type, but this was only significant for lymphoma patients.

For the entire cohort, black race (vs white) and a lack of private insurance (Medicaid, Medicare, uninsured, or unknown insurance status) were significant predictors for a lack of cancer treatment among HIV patients.

Still, the researchers noted that, even among privately insured patients, HIV-infected individuals were less likely to receive cancer treatment.

Dr Suneja and her colleagues said several factors may contribute to these findings. For one, HIV-infected patients have historically been excluded from cancer clinical trials, thereby limiting the applicability of trial results for this population.

In addition, cancer treatment guidelines specific to HIV-infected patients are not available for most cancer types. And clinicians may lack experience treating HIV-infected patients with cancer.

Furthermore, the psychosocial and economic challenges associated with the dual management of cancer and HIV treatment may make adherence to treatment a challenge.

HIV budding from a

cultured lymphocyte

Image courtesy of the CDC

A new study suggests that cancer patients with HIV are less likely to receive cancer treatment, regardless of insurance status and comorbidities.

Patients with HIV were less likely than their HIV-free peers to receive treatment for Hodgkin lymphoma, diffuse large B-cell lymphoma, and 7 solid tumor malignancies.

Gita Suneja, MD, of the University of Utah in Salt Lake City, and her colleagues reported these findings in Cancer.

The team used the National Cancer Data Base to study non-elderly US adults diagnosed with 10 common cancers from 2003 to 2011. There were a total of 10,265 HIV-infected patients and 2,219,232 HIV-free patients.

The researchers examined associations between HIV status and lack of cancer treatment, taking into account insurance status and comorbidities.

The results showed a lack of treatment among HIV patients for all of the cancers studied except anal cancer (relative risk [RR]=1.20, P=0.333).

So HIV-infected patients were more likely to lack cancer treatment for:

• Hodgkin lymphoma (RR=1.92, P<0.001)
• Diffuse large B-cell lymphoma (RR=1.82, P<0.001)
• Head and neck cancer (RR=1.48, P=0.013)
• Upper gastrointestinal tract cancer (RR=2.62, P<0.001)
• Colorectal cancer (RR=1.70, P=0.006)
• Lung cancer (RR=2.46, P<0.001)
• Breast cancer (RR=2.14, P=0.015)
• Cervical cancer (RR=2.81, P<0.001)
• Prostate cancer (RR=2.16, P<0.001).

The researchers said factors that predicted a lack of cancer treatment among HIV-infected individuals varied between those with solid tumors and those with lymphomas.

Advanced stage at the time of cancer diagnosis (stage IV vs stage I) meant HIV patients with solid tumors were less likely to receive cancer treatment, but lymphoma patients were more likely to receive cancer treatment.

Having a higher modified Charlson-Deyo comorbidity score (1 or 2+ vs 0) predicted a lack of cancer treatment for HIV-infected patients with lymphoma but not those with solid tumors.

And older age (45-64 vs 18-44) was associated with a lack of treatment for HIV-infected patients regardless of cancer type, but this was only significant for lymphoma patients.

For the entire cohort, black race (vs white) and a lack of private insurance (Medicaid, Medicare, uninsured, or unknown insurance status) were significant predictors for a lack of cancer treatment among HIV patients.

Still, the researchers noted that, even among privately insured patients, HIV-infected individuals were less likely to receive cancer treatment.

Dr Suneja and her colleagues said several factors may contribute to these findings. For one, HIV-infected patients have historically been excluded from cancer clinical trials, thereby limiting the applicability of trial results for this population.

In addition, cancer treatment guidelines specific to HIV-infected patients are not available for most cancer types. And clinicians may lack experience treating HIV-infected patients with cancer.

Furthermore, the psychosocial and economic challenges associated with the dual management of cancer and HIV treatment may make adherence to treatment a challenge.

Nivolumab (Opdivo)

Photo courtesy of Business Wire

The US Food and Drug Administration (FDA) has granted accelerated approval for the PD-1 inhibitor nivolumab (Opdivo) to treat classical Hodgkin lymphoma (cHL).

The drug is approved to treat patients with relapsed or refractory cHL who have received an autologous hematopoietic stem cell transplant (HSCT) and post-transplant brentuximab vedotin.

Nivolumab received accelerated approval because it has not yet shown a clinical benefit in these patients. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of nivolumab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted nivolumab breakthrough therapy designation, priority review status, and orphan drug designation.

Dosing and precautions

The recommended dose and schedule of nivolumab for cHL patients is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

The FDA added a new “Warning and Precaution” to the label for nivolumab, regarding complications of allogeneic HSCT after nivolumab.

Transplant-related deaths have occurred. So the FDA said healthcare professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.

The FDA has required the manufacturer of nivolumab, Bristol-Myers Squibb, to further study the safety of allogeneic HSCT after nivolumab.

Full prescribing information for the drug is available here.

Trials of nivolumab

The FDA granted nivolumab accelerated approval in cHL patients based on the results of 2 single-arm, multicenter trials—the phase 1 Checkmate 039 trial (presented at ICML last year) and the phase 2 CheckMate 205 trial (to be presented at ASCO 2016).

Efficacy

Thus far, researchers have evaluated the efficacy of nivolumab in 95 cHL patients from both trials. All of these patients previously received an autologous HSCT and post-transplant brentuximab vedotin. They received a median of 5 prior systemic regimens (range, 3 to 15).

The patients received a median of 17 doses of nivolumab (range, 3 to 48). The overall response rate was 65%, and the complete response rate was 7%.

The median time to response was 2.1 months (range, 0.7 to 5.7), and the estimated median duration of response was 8.7 months (range, 0+ to 23.1+).

Safety

Researchers evaluated the safety of nivolumab in 263 patients with relapsed or refractory cHL. Ninety-eight percent of these patients had received an autologous HSCT.  The patients received a median of 10 doses of nivolumab (range, 1 to 48) at the approved dose and schedule.

The most common (≥20%) adverse events (AEs) of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea.

Additional common (≥10%) AEs included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Serious AEs were reported in 21% of patients. The most common, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

Nivolumab (Opdivo)

Photo courtesy of Business Wire

The US Food and Drug Administration (FDA) has granted accelerated approval for the PD-1 inhibitor nivolumab (Opdivo) to treat classical Hodgkin lymphoma (cHL).

The drug is approved to treat patients with relapsed or refractory cHL who have received an autologous hematopoietic stem cell transplant (HSCT) and post-transplant brentuximab vedotin.

Nivolumab received accelerated approval because it has not yet shown a clinical benefit in these patients. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of nivolumab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted nivolumab breakthrough therapy designation, priority review status, and orphan drug designation.

Dosing and precautions

The recommended dose and schedule of nivolumab for cHL patients is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

The FDA added a new “Warning and Precaution” to the label for nivolumab, regarding complications of allogeneic HSCT after nivolumab.

Transplant-related deaths have occurred. So the FDA said healthcare professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.

The FDA has required the manufacturer of nivolumab, Bristol-Myers Squibb, to further study the safety of allogeneic HSCT after nivolumab.

Full prescribing information for the drug is available here.

Trials of nivolumab

The FDA granted nivolumab accelerated approval in cHL patients based on the results of 2 single-arm, multicenter trials—the phase 1 Checkmate 039 trial (presented at ICML last year) and the phase 2 CheckMate 205 trial (to be presented at ASCO 2016).

Efficacy

Thus far, researchers have evaluated the efficacy of nivolumab in 95 cHL patients from both trials. All of these patients previously received an autologous HSCT and post-transplant brentuximab vedotin. They received a median of 5 prior systemic regimens (range, 3 to 15).

The patients received a median of 17 doses of nivolumab (range, 3 to 48). The overall response rate was 65%, and the complete response rate was 7%.

The median time to response was 2.1 months (range, 0.7 to 5.7), and the estimated median duration of response was 8.7 months (range, 0+ to 23.1+).

Safety

Researchers evaluated the safety of nivolumab in 263 patients with relapsed or refractory cHL. Ninety-eight percent of these patients had received an autologous HSCT.  The patients received a median of 10 doses of nivolumab (range, 1 to 48) at the approved dose and schedule.

The most common (≥20%) adverse events (AEs) of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea.

Additional common (≥10%) AEs included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Serious AEs were reported in 21% of patients. The most common, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

Nivolumab (Opdivo)

Photo courtesy of Business Wire

The US Food and Drug Administration (FDA) has granted accelerated approval for the PD-1 inhibitor nivolumab (Opdivo) to treat classical Hodgkin lymphoma (cHL).

The drug is approved to treat patients with relapsed or refractory cHL who have received an autologous hematopoietic stem cell transplant (HSCT) and post-transplant brentuximab vedotin.

Nivolumab received accelerated approval because it has not yet shown a clinical benefit in these patients. The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit. Continued approval of nivolumab for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted nivolumab breakthrough therapy designation, priority review status, and orphan drug designation.

Dosing and precautions

The recommended dose and schedule of nivolumab for cHL patients is 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.

The FDA added a new “Warning and Precaution” to the label for nivolumab, regarding complications of allogeneic HSCT after nivolumab.

Transplant-related deaths have occurred. So the FDA said healthcare professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.

The FDA has required the manufacturer of nivolumab, Bristol-Myers Squibb, to further study the safety of allogeneic HSCT after nivolumab.

Full prescribing information for the drug is available here.

Trials of nivolumab

The FDA granted nivolumab accelerated approval in cHL patients based on the results of 2 single-arm, multicenter trials—the phase 1 Checkmate 039 trial (presented at ICML last year) and the phase 2 CheckMate 205 trial (to be presented at ASCO 2016).

Efficacy

Thus far, researchers have evaluated the efficacy of nivolumab in 95 cHL patients from both trials. All of these patients previously received an autologous HSCT and post-transplant brentuximab vedotin. They received a median of 5 prior systemic regimens (range, 3 to 15).

The patients received a median of 17 doses of nivolumab (range, 3 to 48). The overall response rate was 65%, and the complete response rate was 7%.

The median time to response was 2.1 months (range, 0.7 to 5.7), and the estimated median duration of response was 8.7 months (range, 0+ to 23.1+).

Safety

Researchers evaluated the safety of nivolumab in 263 patients with relapsed or refractory cHL. Ninety-eight percent of these patients had received an autologous HSCT.  The patients received a median of 10 doses of nivolumab (range, 1 to 48) at the approved dose and schedule.

The most common (≥20%) adverse events (AEs) of any grade were fatigue, upper respiratory tract infection, cough, pyrexia, and diarrhea.

Additional common (≥10%) AEs included rash, pruritus, musculoskeletal pain, nausea, vomiting, abdominal pain, headache, peripheral neuropathy, arthralgia, dyspnea, infusion-related reactions, and hypothyroidism or thyroiditis.

Serious AEs were reported in 21% of patients. The most common, reported in 1% to 3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

The Food and Drug Administration has granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and posttransplantation brentuximab vedotin.

Approval was based on a 65% objective response rate in 95 patients treated with nivolumab following autologous HSCT and posttransplantation brentuximab vedotin. All patients in the single-arm, multicenter trial had relapsed or refractory cHL and were enrolled regardless of PD-L1 expression status. Patients received a median of 17 doses of nivolumab, the FDA said in a written statement.

The median time to response was 2.1 months (range, 0.7-5.7 months). The estimated median duration of response was 8.7 months.

The FDA also issued a warning for complications of allogeneic HSCT after nivolumab, reporting that transplant-related deaths have occurred. Health care professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions, they said.

The most common adverse reactions in a second single-arm study used to evaluate safety (n = 263) were upper respiratory tract infection, cough, pyrexia, and diarrhea. Other immune-mediated adverse reactions, occurring in 1%-5% of patients, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. The most common serious adverse reactions, which were reported in 1%-3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

Nivolumab is marketed as Opdivo by Bristol-Myers Squibb and has been previously approved to treat advanced renal cell carcinoma, lung cancer, and melanoma.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and posttransplantation brentuximab vedotin.

Approval was based on a 65% objective response rate in 95 patients treated with nivolumab following autologous HSCT and posttransplantation brentuximab vedotin. All patients in the single-arm, multicenter trial had relapsed or refractory cHL and were enrolled regardless of PD-L1 expression status. Patients received a median of 17 doses of nivolumab, the FDA said in a written statement.

The median time to response was 2.1 months (range, 0.7-5.7 months). The estimated median duration of response was 8.7 months.

The FDA also issued a warning for complications of allogeneic HSCT after nivolumab, reporting that transplant-related deaths have occurred. Health care professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions, they said.

The most common adverse reactions in a second single-arm study used to evaluate safety (n = 263) were upper respiratory tract infection, cough, pyrexia, and diarrhea. Other immune-mediated adverse reactions, occurring in 1%-5% of patients, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. The most common serious adverse reactions, which were reported in 1%-3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

Nivolumab is marketed as Opdivo by Bristol-Myers Squibb and has been previously approved to treat advanced renal cell carcinoma, lung cancer, and melanoma.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has granted accelerated approval to nivolumab for the treatment of patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and posttransplantation brentuximab vedotin.

Approval was based on a 65% objective response rate in 95 patients treated with nivolumab following autologous HSCT and posttransplantation brentuximab vedotin. All patients in the single-arm, multicenter trial had relapsed or refractory cHL and were enrolled regardless of PD-L1 expression status. Patients received a median of 17 doses of nivolumab, the FDA said in a written statement.

The median time to response was 2.1 months (range, 0.7-5.7 months). The estimated median duration of response was 8.7 months.

The FDA also issued a warning for complications of allogeneic HSCT after nivolumab, reporting that transplant-related deaths have occurred. Health care professionals should follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions, they said.

The most common adverse reactions in a second single-arm study used to evaluate safety (n = 263) were upper respiratory tract infection, cough, pyrexia, and diarrhea. Other immune-mediated adverse reactions, occurring in 1%-5% of patients, included rash, pneumonitis, hepatitis, hyperthyroidism, and colitis. The most common serious adverse reactions, which were reported in 1%-3% of patients, were pneumonia, pleural effusion, pneumonitis, pyrexia, infusion-related reaction, and rash.

Nivolumab is marketed as Opdivo by Bristol-Myers Squibb and has been previously approved to treat advanced renal cell carcinoma, lung cancer, and melanoma.

[email protected]

On Twitter @NikolaidesLaura

Fewer than 8% of cases of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) transformed to diffuse large B-cell lymphoma (DLBCL), based on a large prospective single-center study with long-term follow-up.

This rate was lower than the risk of transformation reported for transformed follicular lymphoma or chronic lymphocytic leukemia, according to Dr. Saad Kenderian and his associates at the Mayo Clinic, Rochester, Minn. Transformation was significantly associated with splenic involvement at presentation and with prior chemotherapy exposure, but did not worsen overall survival, they added.

WikimediaCommons/Copyright © 2011 Michael Bonert.

“To our knowledge, this cohort represents the largest analysis to date of consecutive patients with NLPHL,” they said.

The study comprised 222 patients with newly diagnosed NLPHL who were treated at Mayo Clinic between 1970 and 2011. Median age at diagnosis was 40 years, and two-thirds of patients were men. The median follow-up period was 16 years (Blood 2016;12:1960-6. doi: 10.1182/blood-2015-08-665505).

During follow up, 17 cases (7.6%) transformed to DLBCL, for a transformation rate of 0.74 cases for every 100 patient-years, the investigators said. Median time to transformation was 35 months (range, 6-268 months). Predictors of transformation included any prior chemotherapy exposure (P = .04) and splenic involvement (P = .03). The rates of 40-year freedom from transformation were 87% when there was no splenic involvement and 21% when the spleen was involved, and were 87% if radiation therapy was used as a single modality compared with 77% in patients treated with prior chemotherapy or chemoradiation.

Five-year overall survival was 76% in patients with transformed disease, which was similar to overall survival among patients whose disease did not transform to DLBCL, the researchers noted.

Other studies of NLPHL have reported anywhere from a 2% to a 17% transformation rate, but those studies had smaller sample sizes, shorter follow-up periods, and less rigorous enrollment criteria and methods to confirm transformation, the investigators noted. “The finding of splenic involvement as a risk factor for transformation was reported by previous investigators. Interestingly, the association between exposure to prior chemotherapy and reduced freedom from transformation has not been reported in the past, but it has been observed in other low-grade lymphoma studies,” they added. “In contrast to follicular lymphoma, transformed NLPHL is not associated with an adverse impact on OS, suggesting a possibly different biology of transformation.”

The research was partially supported by Lymphoma SPORE and the Predolin Foundation. The investigators had no disclosures.

Fewer than 8% of cases of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) transformed to diffuse large B-cell lymphoma (DLBCL), based on a large prospective single-center study with long-term follow-up.

This rate was lower than the risk of transformation reported for transformed follicular lymphoma or chronic lymphocytic leukemia, according to Dr. Saad Kenderian and his associates at the Mayo Clinic, Rochester, Minn. Transformation was significantly associated with splenic involvement at presentation and with prior chemotherapy exposure, but did not worsen overall survival, they added.

WikimediaCommons/Copyright © 2011 Michael Bonert.

“To our knowledge, this cohort represents the largest analysis to date of consecutive patients with NLPHL,” they said.

The study comprised 222 patients with newly diagnosed NLPHL who were treated at Mayo Clinic between 1970 and 2011. Median age at diagnosis was 40 years, and two-thirds of patients were men. The median follow-up period was 16 years (Blood 2016;12:1960-6. doi: 10.1182/blood-2015-08-665505).

During follow up, 17 cases (7.6%) transformed to DLBCL, for a transformation rate of 0.74 cases for every 100 patient-years, the investigators said. Median time to transformation was 35 months (range, 6-268 months). Predictors of transformation included any prior chemotherapy exposure (P = .04) and splenic involvement (P = .03). The rates of 40-year freedom from transformation were 87% when there was no splenic involvement and 21% when the spleen was involved, and were 87% if radiation therapy was used as a single modality compared with 77% in patients treated with prior chemotherapy or chemoradiation.

Five-year overall survival was 76% in patients with transformed disease, which was similar to overall survival among patients whose disease did not transform to DLBCL, the researchers noted.

Other studies of NLPHL have reported anywhere from a 2% to a 17% transformation rate, but those studies had smaller sample sizes, shorter follow-up periods, and less rigorous enrollment criteria and methods to confirm transformation, the investigators noted. “The finding of splenic involvement as a risk factor for transformation was reported by previous investigators. Interestingly, the association between exposure to prior chemotherapy and reduced freedom from transformation has not been reported in the past, but it has been observed in other low-grade lymphoma studies,” they added. “In contrast to follicular lymphoma, transformed NLPHL is not associated with an adverse impact on OS, suggesting a possibly different biology of transformation.”

The research was partially supported by Lymphoma SPORE and the Predolin Foundation. The investigators had no disclosures.

Fewer than 8% of cases of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) transformed to diffuse large B-cell lymphoma (DLBCL), based on a large prospective single-center study with long-term follow-up.

This rate was lower than the risk of transformation reported for transformed follicular lymphoma or chronic lymphocytic leukemia, according to Dr. Saad Kenderian and his associates at the Mayo Clinic, Rochester, Minn. Transformation was significantly associated with splenic involvement at presentation and with prior chemotherapy exposure, but did not worsen overall survival, they added.

WikimediaCommons/Copyright © 2011 Michael Bonert.

“To our knowledge, this cohort represents the largest analysis to date of consecutive patients with NLPHL,” they said.

The study comprised 222 patients with newly diagnosed NLPHL who were treated at Mayo Clinic between 1970 and 2011. Median age at diagnosis was 40 years, and two-thirds of patients were men. The median follow-up period was 16 years (Blood 2016;12:1960-6. doi: 10.1182/blood-2015-08-665505).

During follow up, 17 cases (7.6%) transformed to DLBCL, for a transformation rate of 0.74 cases for every 100 patient-years, the investigators said. Median time to transformation was 35 months (range, 6-268 months). Predictors of transformation included any prior chemotherapy exposure (P = .04) and splenic involvement (P = .03). The rates of 40-year freedom from transformation were 87% when there was no splenic involvement and 21% when the spleen was involved, and were 87% if radiation therapy was used as a single modality compared with 77% in patients treated with prior chemotherapy or chemoradiation.

Five-year overall survival was 76% in patients with transformed disease, which was similar to overall survival among patients whose disease did not transform to DLBCL, the researchers noted.

Other studies of NLPHL have reported anywhere from a 2% to a 17% transformation rate, but those studies had smaller sample sizes, shorter follow-up periods, and less rigorous enrollment criteria and methods to confirm transformation, the investigators noted. “The finding of splenic involvement as a risk factor for transformation was reported by previous investigators. Interestingly, the association between exposure to prior chemotherapy and reduced freedom from transformation has not been reported in the past, but it has been observed in other low-grade lymphoma studies,” they added. “In contrast to follicular lymphoma, transformed NLPHL is not associated with an adverse impact on OS, suggesting a possibly different biology of transformation.”

The research was partially supported by Lymphoma SPORE and the Predolin Foundation. The investigators had no disclosures.

Pregnant woman

Photo by Nina Matthews

New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.

The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.

However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).

Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.

The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.

The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.

To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.

For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.

When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.

For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.

For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.

The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.

These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.

Pregnant woman

Photo by Nina Matthews

New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.

The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.

However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).

Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.

The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.

The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.

To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.

For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.

When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.

For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.

For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.

The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.

These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.

Pregnant woman

Photo by Nina Matthews

New research suggests a mother’s birthplace may affect the risk of certain cancers for Hispanic children.

The study showed that children of Hispanic mothers who were not born in the US had lower risks of brain cancers, neuroblastoma, and Wilms tumor, when compared to children of US-born Hispanic mothers and non-Hispanic white mothers born in the US.

However, all Hispanic children, regardless of where their mothers were born, had higher risks of acute leukemias and Hodgkin lymphoma but a lower risk of non-Hodgkin lymphoma (NHL).

Julia E. Heck, PhD, of the University of California, Los Angeles, and her colleagues reported these findings in JAMA Pediatrics.

The researchers used California birth records to identify children born from 1983 through 2011. Information on cancer cases came from California Cancer Registry records from 1988 to 2012.

The team restricted their analysis to children of US-born white, US-born Hispanic, and non-US-born Hispanic mothers. The study included 13,666 cases of children diagnosed with cancer before the age of 6 and 15,513,718 children who served as control subjects.

To assess the hazard ratios (HRs) for various cancers, the researchers used children of non-Hispanic white mothers as a reference (HR=1.00) and compared them to the children of non-US-born Hispanic mothers and US-born Hispanic mothers.

For children of non-US-born Hispanic mothers, the HR was 0.50 for glioma, 0.43 for astrocytoma, 0.47 for neuroblastoma, and 0.70 for Wilms tumor. For children of US-born Hispanic mothers, the HR was 0.71 for glioma, 0.62 for astrocytoma, 0.66 for neuroblastoma, and 0.88 for Wilms tumor.

When compared to non-Hispanic white children, Hispanic children had an increased risk of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and Hodgkin lymphoma but lower risks of NHL and Burkitt lymphoma.

For children of US-born Hispanic mothers, the HR was 1.20 for ALL, 1.28 for AML, 2.49 for Hodgkin lymphoma, 0.79 for NHL, and 0.69 for Burkitt lymphoma.

For children of non-US-born Hispanic mothers, the HR was 1.06 for ALL, 1.05 for AML, 2.35 for Hodgkin lymphoma, 0.76 for NHL, and 0.73 for Burkitt lymphoma.

The researchers said the differences observed between children of US-born and non-US-born Hispanic mothers may be explained by lifestyle differences and varying environmental exposures.

These factors may explain the differences in cancer incidence between Hispanic children and white children as well, but the differences may also be a result of genetic variation and infection exposures early in life.