Hodgkin Lymphoma

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved the leukocyte growth factor Nivestym™ (filgrastim-aafi), a biosimilar to Neupogen (filgrastim).

Nivestym is approved to treat patients with nonmyeloid malignancies who are receiving myelosuppressive chemotherapy or undergoing bone marrow transplant, acute myeloid leukemia patients receiving induction or consolidation chemotherapy, patients undergoing autologous peripheral blood progenitor cell collection, and patients with severe chronic neutropenia.

The FDA’s approval of Nivestym was based on a review of evidence suggesting the drug is highly similar to Neupogen, according to Pfizer, the company developing Nivestym.

The full approved indication for Nivestym is as follows:

• To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
• To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in patients with acute myeloid leukemia
• To reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg, febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplant
• For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis
• For chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

For more details on Nivestym, see the full prescribing information.

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

Photo by Rhoda Baer

A review of data from more than 19 million people indicates that diabetes significantly raises a person’s risk of developing cancer.

When researchers compared patients with diabetes and without, both male and female diabetics had an increased risk of leukemias and lymphomas as well as certain solid tumors.

Researchers also found that diabetes conferred a higher cancer risk for women than men, both for all cancers combined and for some specific cancers, including leukemia.

“The link between diabetes and the risk of developing cancer is now firmly established,” said Toshiaki Ohkuma, PhD, of The George Institute for Global Health at the University of New South Wales in Australia.

“We have also demonstrated, for the first time, that women with diabetes are more likely to develop any form of cancer and have a significantly higher chance of developing kidney, oral, and stomach cancers and leukemia.”

Dr Ohkuma and his colleagues reported these findings in Diabetologia.

The researchers conducted a systematic search in PubMed MEDLINE to identify reports on the links between diabetes and cancer. Additional reports were identified from the reference lists of the relevant studies.

Only those cohort studies providing relative risks (RRs) for the association between diabetes and cancer for both women and men were included. In total, 107 relevant articles were identified, along with 36 cohorts of individual participant data.

RRs for cancer were obtained for patients with diabetes (types 1 and 2 combined) versus those without diabetes, for both men and women. The women-to-men ratios of these relative risk ratios (RRRs) were then calculated to determine the excess risk in women if present.

Data on all-site cancer was available from 47 studies, involving 121 cohorts and 19,239,302 individuals.

Diabetics vs non-diabetics

Women with diabetes had a 27% higher risk of all-site cancer compared to women without diabetes (RR=1.27; 95% CI 1.21, 1.32; P<0.001).

For men, the risk of all-site cancer was 19% higher among those with diabetes than those without (RR=1.19; 95% CI 1.13, 1.25; P<0.001).

There were several hematologic malignancies for which diabetics had an increased risk, as shown in the following table.

Sex comparison

Calculation of the women-to-men ratio revealed that women with diabetes had a 6% greater excess risk of all-site cancer compared to men with diabetes (RRR=1.06; 95% CI 1.03, 1.09; P<0.001).

The women-to-men ratios also showed significantly higher risks for female diabetics for:

• Kidney cancer—RRR=1.11 (99% CI 1.04, 1.18; P<0.001)
• Oral cancer—RRR=1.13 (99% CI 1.00, 1.28; P=0.009)
• Stomach cancer—RRR=1.14 (99% CI 1.07, 1.22; P<0.001)
• Leukemia—RRR=1.15 (99% CI 1.02, 1.28; P=0.002).

However, women had a significantly lower risk of liver cancer (RRR=0.88; 99% CI 0.79, 0.99; P=0.005).

There are several possible reasons for the excess cancer risk observed in women, according to study author Sanne Peters, PhD, of The George Institute for Global Health at the University of Oxford in the UK.

For example, on average, women are in the pre-diabetic state of impaired glucose tolerance 2 years longer than men.

“Historically, we know that women are often under-treated when they first present with symptoms of diabetes, are less likely to receive intensive care, and are not taking the same levels of medications as men,” Dr Peters said. “All of these could go some way into explaining why women are at greater risk of developing cancer, but, without more research, we can’t be certain.”

CHICAGO – Positron emission tomography (PET) performed after two cycles of BEACOPP could help identify a subset of advanced-stage Hodgkin lymphoma patients who can receive de-escalated treatment without compromising disease control, results of a phase 3 randomized trial show.

Five-year progression-free survival (PFS) exceeded 85% not only for patients receiving six cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) but also for patients who were de-escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy based on negative PET results, according to the final analysis of the AHL2011 LYSA study, presented at the annual meeting of the American Society of Clinical Oncology.

“This approach allows us to significantly reduce the treatment-related toxicity in most patients, and provides similar patient outcomes compared to standard BEACOPP escalated treatment,” said Olivier Casasnovas, MD, of the University Hospital Le Bocage and Inserm, Dijon, France.

Previous studies have shown that BEACOPP may improve PFS, compared with ABVD, but is more toxic and associated with a higher risk of infertility and myelodysplasia or acute leukemia. Dr. Casasnovas and his colleagues sought to evaluate whether upfront BEACOPP followed by de-escalation to ABVD, when warranted by negative PET results, would improve outcomes without compromising efficacy.

The AHL2011 LYSA study included 823 patients (median age, 30 years; 63% male) with previously untreated advanced classical Hodgkin lymphoma. All patients received PET at baseline, after cycle two of chemotherapy, and again after cycle four.

Patients were randomized either to six cycles of escalated BEACOPP, or to an experimental arm in which patients started with BEACOPP but were de-escalated to ABVD if PET results were negative after two or four cycles of treatment.

PET results after cycle two were negative for 87% of patients in the experimental arm, so on an intent-to-treat basis, 84% of them received two cycles of BEACOPP and four cycles of ABVD, Dr. Casasnovas reported.

PFS, with a median follow-up of 50.4 months, was not significantly different for the standard versus the experimental arm (hazard ratio, 1.084; 95% confidence interval, 0.73-1.59; P = .68). Five-year PFS was 85.7% in the experimental treatment de-escalation arm, compared with 86.2% in the standard arm.

Overall survival was likewise similar between arms, with 5-year overall survival exceeding 95% in both groups, Dr. Casasnovas said.

Although there was no significant difference overall in the incidence of adverse events, there was significantly less anemia, febrile neutropenia, thrombocytopenia, and sepsis in the PET-driven de-escalation arm. Overall, 27% of patients in the standard chemotherapy arm experienced at least one serious adverse event, compared with 17% in the PET-driven arm (P less than .002).

The incidence of second primary malignancies was numerically lower in the experimental arm (1.2% vs. 2.4%), though that finding did not reach statistical significance.

On multivariate analysis, interim PET positivity after cycle two was associated with increased risk of disease progression for patients in this study (HR, 3.316). Risk of progression was even higher for patients with PET positivity after four cycles (HR, 12.968), identifying a subset of patients with “particularly poor outcome” who could benefit from development of new treatment options, Dr. Casasnovas said.

Dr. Casasnovas reported financial ties to AbbVie, Bristol-Myers Squibb, Celgene, Gilead Sciences, Janssen, Merck, Roche/Genentech, Sanofi, and Takeda.

SOURCE: Casasnovas O et al. ASCO 2018, Abstract 7503.

CHICAGO – Positron emission tomography (PET) performed after two cycles of BEACOPP could help identify a subset of advanced-stage Hodgkin lymphoma patients who can receive de-escalated treatment without compromising disease control, results of a phase 3 randomized trial show.

Five-year progression-free survival (PFS) exceeded 85% not only for patients receiving six cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) but also for patients who were de-escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy based on negative PET results, according to the final analysis of the AHL2011 LYSA study, presented at the annual meeting of the American Society of Clinical Oncology.

“This approach allows us to significantly reduce the treatment-related toxicity in most patients, and provides similar patient outcomes compared to standard BEACOPP escalated treatment,” said Olivier Casasnovas, MD, of the University Hospital Le Bocage and Inserm, Dijon, France.

Previous studies have shown that BEACOPP may improve PFS, compared with ABVD, but is more toxic and associated with a higher risk of infertility and myelodysplasia or acute leukemia. Dr. Casasnovas and his colleagues sought to evaluate whether upfront BEACOPP followed by de-escalation to ABVD, when warranted by negative PET results, would improve outcomes without compromising efficacy.

The AHL2011 LYSA study included 823 patients (median age, 30 years; 63% male) with previously untreated advanced classical Hodgkin lymphoma. All patients received PET at baseline, after cycle two of chemotherapy, and again after cycle four.

Patients were randomized either to six cycles of escalated BEACOPP, or to an experimental arm in which patients started with BEACOPP but were de-escalated to ABVD if PET results were negative after two or four cycles of treatment.

PET results after cycle two were negative for 87% of patients in the experimental arm, so on an intent-to-treat basis, 84% of them received two cycles of BEACOPP and four cycles of ABVD, Dr. Casasnovas reported.

PFS, with a median follow-up of 50.4 months, was not significantly different for the standard versus the experimental arm (hazard ratio, 1.084; 95% confidence interval, 0.73-1.59; P = .68). Five-year PFS was 85.7% in the experimental treatment de-escalation arm, compared with 86.2% in the standard arm.

Overall survival was likewise similar between arms, with 5-year overall survival exceeding 95% in both groups, Dr. Casasnovas said.

Although there was no significant difference overall in the incidence of adverse events, there was significantly less anemia, febrile neutropenia, thrombocytopenia, and sepsis in the PET-driven de-escalation arm. Overall, 27% of patients in the standard chemotherapy arm experienced at least one serious adverse event, compared with 17% in the PET-driven arm (P less than .002).

The incidence of second primary malignancies was numerically lower in the experimental arm (1.2% vs. 2.4%), though that finding did not reach statistical significance.

On multivariate analysis, interim PET positivity after cycle two was associated with increased risk of disease progression for patients in this study (HR, 3.316). Risk of progression was even higher for patients with PET positivity after four cycles (HR, 12.968), identifying a subset of patients with “particularly poor outcome” who could benefit from development of new treatment options, Dr. Casasnovas said.

Dr. Casasnovas reported financial ties to AbbVie, Bristol-Myers Squibb, Celgene, Gilead Sciences, Janssen, Merck, Roche/Genentech, Sanofi, and Takeda.

SOURCE: Casasnovas O et al. ASCO 2018, Abstract 7503.

CHICAGO – Positron emission tomography (PET) performed after two cycles of BEACOPP could help identify a subset of advanced-stage Hodgkin lymphoma patients who can receive de-escalated treatment without compromising disease control, results of a phase 3 randomized trial show.

Five-year progression-free survival (PFS) exceeded 85% not only for patients receiving six cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) but also for patients who were de-escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy based on negative PET results, according to the final analysis of the AHL2011 LYSA study, presented at the annual meeting of the American Society of Clinical Oncology.

“This approach allows us to significantly reduce the treatment-related toxicity in most patients, and provides similar patient outcomes compared to standard BEACOPP escalated treatment,” said Olivier Casasnovas, MD, of the University Hospital Le Bocage and Inserm, Dijon, France.

Previous studies have shown that BEACOPP may improve PFS, compared with ABVD, but is more toxic and associated with a higher risk of infertility and myelodysplasia or acute leukemia. Dr. Casasnovas and his colleagues sought to evaluate whether upfront BEACOPP followed by de-escalation to ABVD, when warranted by negative PET results, would improve outcomes without compromising efficacy.

The AHL2011 LYSA study included 823 patients (median age, 30 years; 63% male) with previously untreated advanced classical Hodgkin lymphoma. All patients received PET at baseline, after cycle two of chemotherapy, and again after cycle four.

Patients were randomized either to six cycles of escalated BEACOPP, or to an experimental arm in which patients started with BEACOPP but were de-escalated to ABVD if PET results were negative after two or four cycles of treatment.

PET results after cycle two were negative for 87% of patients in the experimental arm, so on an intent-to-treat basis, 84% of them received two cycles of BEACOPP and four cycles of ABVD, Dr. Casasnovas reported.

PFS, with a median follow-up of 50.4 months, was not significantly different for the standard versus the experimental arm (hazard ratio, 1.084; 95% confidence interval, 0.73-1.59; P = .68). Five-year PFS was 85.7% in the experimental treatment de-escalation arm, compared with 86.2% in the standard arm.

Overall survival was likewise similar between arms, with 5-year overall survival exceeding 95% in both groups, Dr. Casasnovas said.

Although there was no significant difference overall in the incidence of adverse events, there was significantly less anemia, febrile neutropenia, thrombocytopenia, and sepsis in the PET-driven de-escalation arm. Overall, 27% of patients in the standard chemotherapy arm experienced at least one serious adverse event, compared with 17% in the PET-driven arm (P less than .002).

The incidence of second primary malignancies was numerically lower in the experimental arm (1.2% vs. 2.4%), though that finding did not reach statistical significance.

On multivariate analysis, interim PET positivity after cycle two was associated with increased risk of disease progression for patients in this study (HR, 3.316). Risk of progression was even higher for patients with PET positivity after four cycles (HR, 12.968), identifying a subset of patients with “particularly poor outcome” who could benefit from development of new treatment options, Dr. Casasnovas said.

Dr. Casasnovas reported financial ties to AbbVie, Bristol-Myers Squibb, Celgene, Gilead Sciences, Janssen, Merck, Roche/Genentech, Sanofi, and Takeda.

SOURCE: Casasnovas O et al. ASCO 2018, Abstract 7503.

Micrograph showing Hodgkin lymphoma

CHICAGO—Interim PET scans can identify a subset of Hodgkin lymphoma (HL) patients with a better outcome suitable for de-escalation treatment after upfront BEACOPP without impairing disease control, according to final results of the AHL2011-LYSA study.

BEACOPP, compared to ABVD, improves progression-free survival (PFS) but not overall survival (OS) and is associated with a higher risk of myelodysplasia, acute leukemia, and infertility.

Investigators evaluated whether some patients might be able to reduce treatment intensity without compromising the effectiveness of their therapy.

Olivier Casasnovas, MD, of CHU Le Bocage Service d'Hématologie Clinique, Dijon, France,  presented the final analysis at the 2018 ASCO Annual Meeting (abstract 7503).

AHL2011-LYSA study (NCT01358747)

The randomized phase 3 study compared an early PET-driven treatment de-escalation to a non-PET-monitored strategy in patients with advanced-stage HL.

The study included 823 previously untreated patients, median age 30 years (range 16 – 60), with stage III, IV, or high-risk IIB HL.

The PET-driven strategy consisted of 2 BEACOPP* cycles (PET2), followed by 4 cycles of ABVD** for PET2-negative patients, and 4 cycles of BEACOPP for PET2-positive patients.

The experimental PET-driven strategy (410 patients) was randomly compared to a standard treatment delivering 6 cycles of BEACOPP (413 patients). PFS was the primary endpoint with a hypothesis of non-inferiority of the PET-driven arm compared to the standard arm.

Patients characteristics were well balanced between the arms, Dr Casasnovas said. PET2-positivity rate was similar in both arms (experimental 13%, standard 12%).

Based on PET2 results, 346 (84%) patients received 4 cycles of ABVD and 51 (12%) patients received 4 additional cycles of BEACOPP in the experimental arm.

Results

With a median follow-up of 50 months, the 5-year PFS was similar in the standard (86.2%) and the PET-driven arms (85.7%). The 5-year PFS for PET 2-negative/PET 4-negative patients was 90.9%, for PET 2-positive/PET4-negative patients was 75.4%, and for PET 4-positive patients was 46.5%.

The 5-year OS was similar in both arms (96.4% experimental, 95.2% standard).

The treatment toxicity was significantly higher in patients receiving 6 cycles of BEACOPP as compared to those who received 2 cycles of BEACOPP plus 4 cycles of ABVD.

Those who received more cycles of BEACOPP had more frequent grade 3 or higher adverse events than those with fewer cycles, including anemia (11% vs 2%), leukopenia (85% vs 74%), thrombocytopenia (44% vs 15%), and sepsis (7% vs 3%), as well as in serious adverse events (45% vs 28%).

“After 4 cycles of chemotherapy, it [PET positivity] identifies a subset of patients with a particularly poor outcome,” Dr Casasnovas said, “encouraging researchers to develop new treatment options in these patients.”

“PET performed after 2 cycles of BEACOPP escalation can be safely used to guide subsequent treatment,” he concluded.

“This approach allows clinicians to reduce the treatment-related immediate toxicity in most patients,” he added, “and provides similar patient outcomes compared to standard BEACOPP escalation treatment.” 

* Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

**Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine

Micrograph showing Hodgkin lymphoma

CHICAGO—Interim PET scans can identify a subset of Hodgkin lymphoma (HL) patients with a better outcome suitable for de-escalation treatment after upfront BEACOPP without impairing disease control, according to final results of the AHL2011-LYSA study.

BEACOPP, compared to ABVD, improves progression-free survival (PFS) but not overall survival (OS) and is associated with a higher risk of myelodysplasia, acute leukemia, and infertility.

Investigators evaluated whether some patients might be able to reduce treatment intensity without compromising the effectiveness of their therapy.

Olivier Casasnovas, MD, of CHU Le Bocage Service d'Hématologie Clinique, Dijon, France,  presented the final analysis at the 2018 ASCO Annual Meeting (abstract 7503).

AHL2011-LYSA study (NCT01358747)

The randomized phase 3 study compared an early PET-driven treatment de-escalation to a non-PET-monitored strategy in patients with advanced-stage HL.

The study included 823 previously untreated patients, median age 30 years (range 16 – 60), with stage III, IV, or high-risk IIB HL.

The PET-driven strategy consisted of 2 BEACOPP* cycles (PET2), followed by 4 cycles of ABVD** for PET2-negative patients, and 4 cycles of BEACOPP for PET2-positive patients.

The experimental PET-driven strategy (410 patients) was randomly compared to a standard treatment delivering 6 cycles of BEACOPP (413 patients). PFS was the primary endpoint with a hypothesis of non-inferiority of the PET-driven arm compared to the standard arm.

Patients characteristics were well balanced between the arms, Dr Casasnovas said. PET2-positivity rate was similar in both arms (experimental 13%, standard 12%).

Based on PET2 results, 346 (84%) patients received 4 cycles of ABVD and 51 (12%) patients received 4 additional cycles of BEACOPP in the experimental arm.

Results

With a median follow-up of 50 months, the 5-year PFS was similar in the standard (86.2%) and the PET-driven arms (85.7%). The 5-year PFS for PET 2-negative/PET 4-negative patients was 90.9%, for PET 2-positive/PET4-negative patients was 75.4%, and for PET 4-positive patients was 46.5%.

The 5-year OS was similar in both arms (96.4% experimental, 95.2% standard).

The treatment toxicity was significantly higher in patients receiving 6 cycles of BEACOPP as compared to those who received 2 cycles of BEACOPP plus 4 cycles of ABVD.

Those who received more cycles of BEACOPP had more frequent grade 3 or higher adverse events than those with fewer cycles, including anemia (11% vs 2%), leukopenia (85% vs 74%), thrombocytopenia (44% vs 15%), and sepsis (7% vs 3%), as well as in serious adverse events (45% vs 28%).

“After 4 cycles of chemotherapy, it [PET positivity] identifies a subset of patients with a particularly poor outcome,” Dr Casasnovas said, “encouraging researchers to develop new treatment options in these patients.”

“PET performed after 2 cycles of BEACOPP escalation can be safely used to guide subsequent treatment,” he concluded.

“This approach allows clinicians to reduce the treatment-related immediate toxicity in most patients,” he added, “and provides similar patient outcomes compared to standard BEACOPP escalation treatment.” 

* Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

**Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine

Micrograph showing Hodgkin lymphoma

CHICAGO—Interim PET scans can identify a subset of Hodgkin lymphoma (HL) patients with a better outcome suitable for de-escalation treatment after upfront BEACOPP without impairing disease control, according to final results of the AHL2011-LYSA study.

BEACOPP, compared to ABVD, improves progression-free survival (PFS) but not overall survival (OS) and is associated with a higher risk of myelodysplasia, acute leukemia, and infertility.

Investigators evaluated whether some patients might be able to reduce treatment intensity without compromising the effectiveness of their therapy.

Olivier Casasnovas, MD, of CHU Le Bocage Service d'Hématologie Clinique, Dijon, France,  presented the final analysis at the 2018 ASCO Annual Meeting (abstract 7503).

AHL2011-LYSA study (NCT01358747)

The randomized phase 3 study compared an early PET-driven treatment de-escalation to a non-PET-monitored strategy in patients with advanced-stage HL.

The study included 823 previously untreated patients, median age 30 years (range 16 – 60), with stage III, IV, or high-risk IIB HL.

The PET-driven strategy consisted of 2 BEACOPP* cycles (PET2), followed by 4 cycles of ABVD** for PET2-negative patients, and 4 cycles of BEACOPP for PET2-positive patients.

The experimental PET-driven strategy (410 patients) was randomly compared to a standard treatment delivering 6 cycles of BEACOPP (413 patients). PFS was the primary endpoint with a hypothesis of non-inferiority of the PET-driven arm compared to the standard arm.

Patients characteristics were well balanced between the arms, Dr Casasnovas said. PET2-positivity rate was similar in both arms (experimental 13%, standard 12%).

Based on PET2 results, 346 (84%) patients received 4 cycles of ABVD and 51 (12%) patients received 4 additional cycles of BEACOPP in the experimental arm.

Results

With a median follow-up of 50 months, the 5-year PFS was similar in the standard (86.2%) and the PET-driven arms (85.7%). The 5-year PFS for PET 2-negative/PET 4-negative patients was 90.9%, for PET 2-positive/PET4-negative patients was 75.4%, and for PET 4-positive patients was 46.5%.

The 5-year OS was similar in both arms (96.4% experimental, 95.2% standard).

The treatment toxicity was significantly higher in patients receiving 6 cycles of BEACOPP as compared to those who received 2 cycles of BEACOPP plus 4 cycles of ABVD.

Those who received more cycles of BEACOPP had more frequent grade 3 or higher adverse events than those with fewer cycles, including anemia (11% vs 2%), leukopenia (85% vs 74%), thrombocytopenia (44% vs 15%), and sepsis (7% vs 3%), as well as in serious adverse events (45% vs 28%).

“After 4 cycles of chemotherapy, it [PET positivity] identifies a subset of patients with a particularly poor outcome,” Dr Casasnovas said, “encouraging researchers to develop new treatment options in these patients.”

“PET performed after 2 cycles of BEACOPP escalation can be safely used to guide subsequent treatment,” he concluded.

“This approach allows clinicians to reduce the treatment-related immediate toxicity in most patients,” he added, “and provides similar patient outcomes compared to standard BEACOPP escalation treatment.” 

* Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone

**Adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine

A lifetime of physical inactivity could significantly increase the risk of developing both Hodgkin and non-Hodgkin lymphoma, according to a case-control study.

Researchers examined self-reported lifetime physical activity in 87 patients with Hodgkin lymphoma and 236 patients with non-Hodgkin lymphoma, as well as 1,300 cancer-free controls.

pojoslaw/ThinkStock

SOURCE: Etter JL et al. Leuk Res. 2018 Mar 27;69:7-11.

A lifetime of physical inactivity could significantly increase the risk of developing both Hodgkin and non-Hodgkin lymphoma, according to a case-control study.

Researchers examined self-reported lifetime physical activity in 87 patients with Hodgkin lymphoma and 236 patients with non-Hodgkin lymphoma, as well as 1,300 cancer-free controls.

pojoslaw/ThinkStock

SOURCE: Etter JL et al. Leuk Res. 2018 Mar 27;69:7-11.

A lifetime of physical inactivity could significantly increase the risk of developing both Hodgkin and non-Hodgkin lymphoma, according to a case-control study.

Researchers examined self-reported lifetime physical activity in 87 patients with Hodgkin lymphoma and 236 patients with non-Hodgkin lymphoma, as well as 1,300 cancer-free controls.

pojoslaw/ThinkStock

SOURCE: Etter JL et al. Leuk Res. 2018 Mar 27;69:7-11.

Micrograph showing CLL

Phase 1 trial results suggest umbralisib, a PI3Kδ/CK1ε inhibitor, can be safe and active in patients with relapsed or refractory B-cell malignancies.

Researchers said the safety profile of umbralisib “was distinct from that of other PI3Kδ inhibitors,” as it produced few immune-mediated adverse events (AEs).

Umbralisib also produced an objective response rate of 37% in the entire study cohort, 80% in patients with chronic lymphocytic leukemia (CLL), 53% in patients with follicular lymphoma (FL), and 31% in patients with diffuse large B-cell lymphoma (DLBCL).

These results were published in The Lancet Oncology. The study was sponsored by TG Therapeutics, Inc.

The trial enrolled 90 patients between January 17, 2013, and January 14, 2016.

There were 24 patients with CLL, 22 with FL, 16 with DLBCL, 11 with Hodgkin lymphoma, 6 with mantle cell lymphoma, 5 with marginal zone lymphoma, 3 with Waldenstrom’s macroglobulinemia, 2 with T-cell lymphoma, and 1 with hairy cell leukemia.

The median number of prior therapies was 3 (range, 2-5), and 49% of patients were refractory to previous therapy.

Treatment

Patients took umbralisib once daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.

Initially, patients took the drug in a fasting state at doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In April 2014, the researchers did a second dose-escalation with a micronized formulation of umbralisib, taken with food, at doses of 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In August, 2014, all patients who were still on the study transitioned to the 800 mg dose of the micronized formulation. This was the recommended phase 2 dose.

At the data cutoff in November 2016, 44 patients (49%) had received umbralisib for more than 6 cycles, and 23 (26%) had received the drug for more than 12 cycles. Thirteen patients (14%) were still taking umbralisib at the end of the study.

Most patients who stopped treatment did so because of disease progression (n=50, 56%) or AEs (n=9, 10%).

“We are pleased to have treated the first patient ever with umbralisib over 5 years ago and believe it has an important place in the treatment landscape for patients with hematologic malignancies,” said study author Howard A. Burris, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee.

“Several patients from this phase 1 study are still on study today, approaching 5 years of continuous daily therapy, speaking to both the safety and efficacy profile of this unique agent.”

Safety

Dose-limiting toxicities (DLTs) occurred in 4 patients. One DLT was grade 3 maculopapular rash in a patient receiving the 800 mg dose of the initial formulation.

Another DLT was grade 3 hypokalemia in a patient receiving 1800 mg of the initial formulation. A third DLT was grade 3 fatigue, which occurred in 2 patients receiving 1800 mg of the micronized formulation.

Because of these toxicities, the maximum tolerated dose was 1200 mg of the micronized formulation.

The most common treatment-emergent AEs were diarrhea (43%), nausea (42%), and fatigue (31%). The most common grade 3/4 AEs were neutropenia (13%), anemia (9%), and thrombocytopenia (7%).

Serious AEs considered at least possibly related to umbralisib were pneumonia (3%), lung infection (1%), febrile neutropenia (1%), and colitis (2%).

Treatment discontinuation due to AEs considered at least possibly related to umbralisib occurred in 6 patients (7%). Two patients had grade 3 colitis, 2 had increased ALT/AST (grade 1 and grade 4), 1 had grade 2 diarrhea, and 1 had grade 3 fatigue.

There were no treatment-related deaths.

The researchers said the safety profile of umbralisib was distinct from that of other PI3Kδ inhibitors, as patients in this trial had fewer occurrences of autoimmune-like toxicities, such as colitis.

“Preclinically, umbralisib has a very unique profile, selectively inhibiting both PI3Kδ and CK1ε,” said study author Owen O’Connor, MD, PhD, of Columbia Presbyterian Medical Center in New York, New York.

“The clinical results in this paper support our thesis that the differentiated preclinical profile explains the differences seen in the clinic between umbralisib and the other PI3Kδ inhibitors.”

Response

The objective response rate was 37%, with 33 patients achieving a response and 3 patients having a complete response (CR).

Sixteen CLL patients responded (80%), all with partial responses (PRs). Four DLBCL patients responded (31%), all with PRs. And 9 FL patients responded (53%), 2 with CRs.

The remaining CR occurred in a Hodgkin lymphoma patient, and this was the only response in this patient group.

One patient with marginal zone lymphoma had a PR, as did 1 patient with mantle cell lymphoma. All other patients had stable disease or progressed.

The mean duration of response was 13.4 months in the CLL patients, 6.4 months in the DLBCL patients, and 9.3 months in the FL patients.

Micrograph showing CLL

Phase 1 trial results suggest umbralisib, a PI3Kδ/CK1ε inhibitor, can be safe and active in patients with relapsed or refractory B-cell malignancies.

Researchers said the safety profile of umbralisib “was distinct from that of other PI3Kδ inhibitors,” as it produced few immune-mediated adverse events (AEs).

Umbralisib also produced an objective response rate of 37% in the entire study cohort, 80% in patients with chronic lymphocytic leukemia (CLL), 53% in patients with follicular lymphoma (FL), and 31% in patients with diffuse large B-cell lymphoma (DLBCL).

These results were published in The Lancet Oncology. The study was sponsored by TG Therapeutics, Inc.

The trial enrolled 90 patients between January 17, 2013, and January 14, 2016.

There were 24 patients with CLL, 22 with FL, 16 with DLBCL, 11 with Hodgkin lymphoma, 6 with mantle cell lymphoma, 5 with marginal zone lymphoma, 3 with Waldenstrom’s macroglobulinemia, 2 with T-cell lymphoma, and 1 with hairy cell leukemia.

The median number of prior therapies was 3 (range, 2-5), and 49% of patients were refractory to previous therapy.

Treatment

Patients took umbralisib once daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.

Initially, patients took the drug in a fasting state at doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In April 2014, the researchers did a second dose-escalation with a micronized formulation of umbralisib, taken with food, at doses of 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In August, 2014, all patients who were still on the study transitioned to the 800 mg dose of the micronized formulation. This was the recommended phase 2 dose.

At the data cutoff in November 2016, 44 patients (49%) had received umbralisib for more than 6 cycles, and 23 (26%) had received the drug for more than 12 cycles. Thirteen patients (14%) were still taking umbralisib at the end of the study.

Most patients who stopped treatment did so because of disease progression (n=50, 56%) or AEs (n=9, 10%).

“We are pleased to have treated the first patient ever with umbralisib over 5 years ago and believe it has an important place in the treatment landscape for patients with hematologic malignancies,” said study author Howard A. Burris, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee.

“Several patients from this phase 1 study are still on study today, approaching 5 years of continuous daily therapy, speaking to both the safety and efficacy profile of this unique agent.”

Safety

Dose-limiting toxicities (DLTs) occurred in 4 patients. One DLT was grade 3 maculopapular rash in a patient receiving the 800 mg dose of the initial formulation.

Another DLT was grade 3 hypokalemia in a patient receiving 1800 mg of the initial formulation. A third DLT was grade 3 fatigue, which occurred in 2 patients receiving 1800 mg of the micronized formulation.

Because of these toxicities, the maximum tolerated dose was 1200 mg of the micronized formulation.

The most common treatment-emergent AEs were diarrhea (43%), nausea (42%), and fatigue (31%). The most common grade 3/4 AEs were neutropenia (13%), anemia (9%), and thrombocytopenia (7%).

Serious AEs considered at least possibly related to umbralisib were pneumonia (3%), lung infection (1%), febrile neutropenia (1%), and colitis (2%).

Treatment discontinuation due to AEs considered at least possibly related to umbralisib occurred in 6 patients (7%). Two patients had grade 3 colitis, 2 had increased ALT/AST (grade 1 and grade 4), 1 had grade 2 diarrhea, and 1 had grade 3 fatigue.

There were no treatment-related deaths.

The researchers said the safety profile of umbralisib was distinct from that of other PI3Kδ inhibitors, as patients in this trial had fewer occurrences of autoimmune-like toxicities, such as colitis.

“Preclinically, umbralisib has a very unique profile, selectively inhibiting both PI3Kδ and CK1ε,” said study author Owen O’Connor, MD, PhD, of Columbia Presbyterian Medical Center in New York, New York.

“The clinical results in this paper support our thesis that the differentiated preclinical profile explains the differences seen in the clinic between umbralisib and the other PI3Kδ inhibitors.”

Response

The objective response rate was 37%, with 33 patients achieving a response and 3 patients having a complete response (CR).

Sixteen CLL patients responded (80%), all with partial responses (PRs). Four DLBCL patients responded (31%), all with PRs. And 9 FL patients responded (53%), 2 with CRs.

The remaining CR occurred in a Hodgkin lymphoma patient, and this was the only response in this patient group.

One patient with marginal zone lymphoma had a PR, as did 1 patient with mantle cell lymphoma. All other patients had stable disease or progressed.

The mean duration of response was 13.4 months in the CLL patients, 6.4 months in the DLBCL patients, and 9.3 months in the FL patients.

Micrograph showing CLL

Phase 1 trial results suggest umbralisib, a PI3Kδ/CK1ε inhibitor, can be safe and active in patients with relapsed or refractory B-cell malignancies.

Researchers said the safety profile of umbralisib “was distinct from that of other PI3Kδ inhibitors,” as it produced few immune-mediated adverse events (AEs).

Umbralisib also produced an objective response rate of 37% in the entire study cohort, 80% in patients with chronic lymphocytic leukemia (CLL), 53% in patients with follicular lymphoma (FL), and 31% in patients with diffuse large B-cell lymphoma (DLBCL).

These results were published in The Lancet Oncology. The study was sponsored by TG Therapeutics, Inc.

The trial enrolled 90 patients between January 17, 2013, and January 14, 2016.

There were 24 patients with CLL, 22 with FL, 16 with DLBCL, 11 with Hodgkin lymphoma, 6 with mantle cell lymphoma, 5 with marginal zone lymphoma, 3 with Waldenstrom’s macroglobulinemia, 2 with T-cell lymphoma, and 1 with hairy cell leukemia.

The median number of prior therapies was 3 (range, 2-5), and 49% of patients were refractory to previous therapy.

Treatment

Patients took umbralisib once daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent.

Initially, patients took the drug in a fasting state at doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In April 2014, the researchers did a second dose-escalation with a micronized formulation of umbralisib, taken with food, at doses of 200 mg, 400 mg, 800 mg, 1200 mg, or 1800 mg.

In August, 2014, all patients who were still on the study transitioned to the 800 mg dose of the micronized formulation. This was the recommended phase 2 dose.

At the data cutoff in November 2016, 44 patients (49%) had received umbralisib for more than 6 cycles, and 23 (26%) had received the drug for more than 12 cycles. Thirteen patients (14%) were still taking umbralisib at the end of the study.

Most patients who stopped treatment did so because of disease progression (n=50, 56%) or AEs (n=9, 10%).

“We are pleased to have treated the first patient ever with umbralisib over 5 years ago and believe it has an important place in the treatment landscape for patients with hematologic malignancies,” said study author Howard A. Burris, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee.

“Several patients from this phase 1 study are still on study today, approaching 5 years of continuous daily therapy, speaking to both the safety and efficacy profile of this unique agent.”

Safety

Dose-limiting toxicities (DLTs) occurred in 4 patients. One DLT was grade 3 maculopapular rash in a patient receiving the 800 mg dose of the initial formulation.

Another DLT was grade 3 hypokalemia in a patient receiving 1800 mg of the initial formulation. A third DLT was grade 3 fatigue, which occurred in 2 patients receiving 1800 mg of the micronized formulation.

Because of these toxicities, the maximum tolerated dose was 1200 mg of the micronized formulation.

The most common treatment-emergent AEs were diarrhea (43%), nausea (42%), and fatigue (31%). The most common grade 3/4 AEs were neutropenia (13%), anemia (9%), and thrombocytopenia (7%).

Serious AEs considered at least possibly related to umbralisib were pneumonia (3%), lung infection (1%), febrile neutropenia (1%), and colitis (2%).

Treatment discontinuation due to AEs considered at least possibly related to umbralisib occurred in 6 patients (7%). Two patients had grade 3 colitis, 2 had increased ALT/AST (grade 1 and grade 4), 1 had grade 2 diarrhea, and 1 had grade 3 fatigue.

There were no treatment-related deaths.

The researchers said the safety profile of umbralisib was distinct from that of other PI3Kδ inhibitors, as patients in this trial had fewer occurrences of autoimmune-like toxicities, such as colitis.

“Preclinically, umbralisib has a very unique profile, selectively inhibiting both PI3Kδ and CK1ε,” said study author Owen O’Connor, MD, PhD, of Columbia Presbyterian Medical Center in New York, New York.

“The clinical results in this paper support our thesis that the differentiated preclinical profile explains the differences seen in the clinic between umbralisib and the other PI3Kδ inhibitors.”

Response

The objective response rate was 37%, with 33 patients achieving a response and 3 patients having a complete response (CR).

Sixteen CLL patients responded (80%), all with partial responses (PRs). Four DLBCL patients responded (31%), all with PRs. And 9 FL patients responded (53%), 2 with CRs.

The remaining CR occurred in a Hodgkin lymphoma patient, and this was the only response in this patient group.

One patient with marginal zone lymphoma had a PR, as did 1 patient with mantle cell lymphoma. All other patients had stable disease or progressed.

The mean duration of response was 13.4 months in the CLL patients, 6.4 months in the DLBCL patients, and 9.3 months in the FL patients.

Micrograph showing Hodgkin lymphoma

Nivolumab can provide “long-term benefits” in patients with relapsed or refractory classical Hodgkin lymphoma (cHL), according to researchers.

Extended follow-up of the CheckMate-205 study showed that nearly 70% of patients responded to nivolumab.

The median duration of response was 17 months, and the median progression-free survival (PFS) was 15 months.

The most common drug-related AEs were fatigue, diarrhea, infusion-related reactions, rash, nausea, and pruritus.

Philippe Armand, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in the Journal of Clinical Oncology.

The study was sponsored by Bristol-Myers Squibb Company.

Patients

This phase 2 trial enrolled 243 adults with relapsed or refractory cHL who had undergone autologous hematopoietic stem cell transplant (auto-HSCT).

Their median age was 34 (range, 26-46), and 58% were male. Fifty-seven percent had stage IV disease, 20% had stage III, 21% had stage II, and 2% had stage I.

Patients had received a median of 4 prior therapies (range, 3-5). The median time from diagnosis to first nivolumab dose was 4.5 years (range, 2.4-7.6), and the median time from most recent auto-HSCT to first nivolumab dose was 2.0 years (range, 0.9-4.9).

The researchers divided patients into 3 cohorts according to exposure to brentuximab vedotin (BV):

• Cohort A was BV-naïve (n=63)
• Cohort B received BV only after auto-HSCT (n=80)
• Cohort C received BV before and/or after auto-HSCT (n=100).

Baseline characteristics were generally similar across the cohorts. However, cohort A had fewer prior treatments (median of 2 vs 4 in cohorts B and C).

Cohort B had the longest interval between diagnosis and first nivolumab dose (6.2 years vs 3.1 in cohort A and 3.5 in C) and between most recent auto-HSCT and first nivolumab dose (3.4 years vs 1 in cohort A and 1.7 in C).

Treatment

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year had to discontinue nivolumab, but they could resume treatment if they relapsed within 2 years.

A protocol amendment allowed patients to continue treatment despite progression if they had stable performance status and were deriving “perceived clinical benefit.”

At a median follow-up of 18 months, 40% percent of all patients were still on treatment, including 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

Safety

The most common drug-related AEs were fatigue (23%), diarrhea (15%), infusion-related reactions (14%), rash (12%), nausea (10%), and pruritus (10%).

The most common grade 3/4 drug-related AEs were lipase increase (5%), neutropenia (3%), ALT increase (2%), AST increase (2%), and amylase increase (2%).

The most common serious drug-related AEs were infusion-related reactions (2%), pneumonitis (1%), pneumonia (1%), pleural effusion (1%), and pyrexia (1%).

Seven percent of patients discontinued treatment due to AEs. The most common of these were pneumonitis (2%) and autoimmune hepatitis (1%).

There were no deaths due to drug-related AEs.

Efficacy

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, 15 months for cohort C, and 20 months for patients who achieved a CR.

The researchers said responses were similar irrespective of BV treatment sequence.

The median PFS was 15 months for all patients, 18 months for cohort A, 15 months for cohort B, 12 months for cohort C, and 22 months for patients who achieved a CR.

The median overall survival was not reached in any of the cohorts.

The 12-month overall survival was 92% overall, 93% in cohort A, 95% in cohort B, 90% in cohort C, and 100% in patients who achieved a CR.

Subsequent HSCT

Forty-four patients proceeded to allogeneic HSCT after nivolumab, and the median post-HSCT follow-up was 5.5 months (range, 2.9-11.8).

At 6 months, the rate of transplant-related mortality was 13%, and the rate of disease progression was 7%.

The rate of grade 2-4 acute graft-vs-host disease (GVHD) was 30%, the rate of grade 3-4 acute GVHD was 20%, and the rate of chronic GVHD was 15%.

Micrograph showing Hodgkin lymphoma

Nivolumab can provide “long-term benefits” in patients with relapsed or refractory classical Hodgkin lymphoma (cHL), according to researchers.

Extended follow-up of the CheckMate-205 study showed that nearly 70% of patients responded to nivolumab.

The median duration of response was 17 months, and the median progression-free survival (PFS) was 15 months.

The most common drug-related AEs were fatigue, diarrhea, infusion-related reactions, rash, nausea, and pruritus.

Philippe Armand, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in the Journal of Clinical Oncology.

The study was sponsored by Bristol-Myers Squibb Company.

Patients

This phase 2 trial enrolled 243 adults with relapsed or refractory cHL who had undergone autologous hematopoietic stem cell transplant (auto-HSCT).

Their median age was 34 (range, 26-46), and 58% were male. Fifty-seven percent had stage IV disease, 20% had stage III, 21% had stage II, and 2% had stage I.

Patients had received a median of 4 prior therapies (range, 3-5). The median time from diagnosis to first nivolumab dose was 4.5 years (range, 2.4-7.6), and the median time from most recent auto-HSCT to first nivolumab dose was 2.0 years (range, 0.9-4.9).

The researchers divided patients into 3 cohorts according to exposure to brentuximab vedotin (BV):

• Cohort A was BV-naïve (n=63)
• Cohort B received BV only after auto-HSCT (n=80)
• Cohort C received BV before and/or after auto-HSCT (n=100).

Baseline characteristics were generally similar across the cohorts. However, cohort A had fewer prior treatments (median of 2 vs 4 in cohorts B and C).

Cohort B had the longest interval between diagnosis and first nivolumab dose (6.2 years vs 3.1 in cohort A and 3.5 in C) and between most recent auto-HSCT and first nivolumab dose (3.4 years vs 1 in cohort A and 1.7 in C).

Treatment

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year had to discontinue nivolumab, but they could resume treatment if they relapsed within 2 years.

A protocol amendment allowed patients to continue treatment despite progression if they had stable performance status and were deriving “perceived clinical benefit.”

At a median follow-up of 18 months, 40% percent of all patients were still on treatment, including 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

Safety

The most common drug-related AEs were fatigue (23%), diarrhea (15%), infusion-related reactions (14%), rash (12%), nausea (10%), and pruritus (10%).

The most common grade 3/4 drug-related AEs were lipase increase (5%), neutropenia (3%), ALT increase (2%), AST increase (2%), and amylase increase (2%).

The most common serious drug-related AEs were infusion-related reactions (2%), pneumonitis (1%), pneumonia (1%), pleural effusion (1%), and pyrexia (1%).

Seven percent of patients discontinued treatment due to AEs. The most common of these were pneumonitis (2%) and autoimmune hepatitis (1%).

There were no deaths due to drug-related AEs.

Efficacy

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, 15 months for cohort C, and 20 months for patients who achieved a CR.

The researchers said responses were similar irrespective of BV treatment sequence.

The median PFS was 15 months for all patients, 18 months for cohort A, 15 months for cohort B, 12 months for cohort C, and 22 months for patients who achieved a CR.

The median overall survival was not reached in any of the cohorts.

The 12-month overall survival was 92% overall, 93% in cohort A, 95% in cohort B, 90% in cohort C, and 100% in patients who achieved a CR.

Subsequent HSCT

Forty-four patients proceeded to allogeneic HSCT after nivolumab, and the median post-HSCT follow-up was 5.5 months (range, 2.9-11.8).

At 6 months, the rate of transplant-related mortality was 13%, and the rate of disease progression was 7%.

The rate of grade 2-4 acute graft-vs-host disease (GVHD) was 30%, the rate of grade 3-4 acute GVHD was 20%, and the rate of chronic GVHD was 15%.

Micrograph showing Hodgkin lymphoma

Nivolumab can provide “long-term benefits” in patients with relapsed or refractory classical Hodgkin lymphoma (cHL), according to researchers.

Extended follow-up of the CheckMate-205 study showed that nearly 70% of patients responded to nivolumab.

The median duration of response was 17 months, and the median progression-free survival (PFS) was 15 months.

The most common drug-related AEs were fatigue, diarrhea, infusion-related reactions, rash, nausea, and pruritus.

Philippe Armand, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in the Journal of Clinical Oncology.

The study was sponsored by Bristol-Myers Squibb Company.

Patients

This phase 2 trial enrolled 243 adults with relapsed or refractory cHL who had undergone autologous hematopoietic stem cell transplant (auto-HSCT).

Their median age was 34 (range, 26-46), and 58% were male. Fifty-seven percent had stage IV disease, 20% had stage III, 21% had stage II, and 2% had stage I.

Patients had received a median of 4 prior therapies (range, 3-5). The median time from diagnosis to first nivolumab dose was 4.5 years (range, 2.4-7.6), and the median time from most recent auto-HSCT to first nivolumab dose was 2.0 years (range, 0.9-4.9).

The researchers divided patients into 3 cohorts according to exposure to brentuximab vedotin (BV):

• Cohort A was BV-naïve (n=63)
• Cohort B received BV only after auto-HSCT (n=80)
• Cohort C received BV before and/or after auto-HSCT (n=100).

Baseline characteristics were generally similar across the cohorts. However, cohort A had fewer prior treatments (median of 2 vs 4 in cohorts B and C).

Cohort B had the longest interval between diagnosis and first nivolumab dose (6.2 years vs 3.1 in cohort A and 3.5 in C) and between most recent auto-HSCT and first nivolumab dose (3.4 years vs 1 in cohort A and 1.7 in C).

Treatment

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year had to discontinue nivolumab, but they could resume treatment if they relapsed within 2 years.

A protocol amendment allowed patients to continue treatment despite progression if they had stable performance status and were deriving “perceived clinical benefit.”

At a median follow-up of 18 months, 40% percent of all patients were still on treatment, including 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

Safety

The most common drug-related AEs were fatigue (23%), diarrhea (15%), infusion-related reactions (14%), rash (12%), nausea (10%), and pruritus (10%).

The most common grade 3/4 drug-related AEs were lipase increase (5%), neutropenia (3%), ALT increase (2%), AST increase (2%), and amylase increase (2%).

The most common serious drug-related AEs were infusion-related reactions (2%), pneumonitis (1%), pneumonia (1%), pleural effusion (1%), and pyrexia (1%).

Seven percent of patients discontinued treatment due to AEs. The most common of these were pneumonitis (2%) and autoimmune hepatitis (1%).

There were no deaths due to drug-related AEs.

Efficacy

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, 15 months for cohort C, and 20 months for patients who achieved a CR.

The researchers said responses were similar irrespective of BV treatment sequence.

The median PFS was 15 months for all patients, 18 months for cohort A, 15 months for cohort B, 12 months for cohort C, and 22 months for patients who achieved a CR.

The median overall survival was not reached in any of the cohorts.

The 12-month overall survival was 92% overall, 93% in cohort A, 95% in cohort B, 90% in cohort C, and 100% in patients who achieved a CR.

Subsequent HSCT

Forty-four patients proceeded to allogeneic HSCT after nivolumab, and the median post-HSCT follow-up was 5.5 months (range, 2.9-11.8).

At 6 months, the rate of transplant-related mortality was 13%, and the rate of disease progression was 7%.

The rate of grade 2-4 acute graft-vs-host disease (GVHD) was 30%, the rate of grade 3-4 acute GVHD was 20%, and the rate of chronic GVHD was 15%.

ORLANDO – Not all oncology drugs are equal when it comes to their risk of treatment-induced cardiac arrhythmias.

Indeed, compared with anthracycline-based regimens, long the workhorse in treating many forms of cancer, the novel targeted agents – tyrosine kinase inhibitors, immune checkpoint inhibitors, and monoclonal antibodies – were 40% less likely to result in a new arrhythmia diagnosis within 6 months of treatment initiation, in a large, single-center retrospective study reported by Andrew Nickel at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

[email protected]

SOURCE: Nickel A et al. ACC 18. Abstract 900-06.

ORLANDO – Not all oncology drugs are equal when it comes to their risk of treatment-induced cardiac arrhythmias.

Indeed, compared with anthracycline-based regimens, long the workhorse in treating many forms of cancer, the novel targeted agents – tyrosine kinase inhibitors, immune checkpoint inhibitors, and monoclonal antibodies – were 40% less likely to result in a new arrhythmia diagnosis within 6 months of treatment initiation, in a large, single-center retrospective study reported by Andrew Nickel at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

[email protected]

SOURCE: Nickel A et al. ACC 18. Abstract 900-06.

ORLANDO – Not all oncology drugs are equal when it comes to their risk of treatment-induced cardiac arrhythmias.

Indeed, compared with anthracycline-based regimens, long the workhorse in treating many forms of cancer, the novel targeted agents – tyrosine kinase inhibitors, immune checkpoint inhibitors, and monoclonal antibodies – were 40% less likely to result in a new arrhythmia diagnosis within 6 months of treatment initiation, in a large, single-center retrospective study reported by Andrew Nickel at the annual meeting of the American College of Cardiology.

Bruce Jancin/MDedge News

[email protected]

SOURCE: Nickel A et al. ACC 18. Abstract 900-06.

Hodgkin lymphoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion of Carmustine Obvius, a generic version of Carmubris.

The CHMP is recommending marketing authorization for Carmustine Obvius as second-line treatment for Hodgkin and non-Hodgkin lymphoma as well as to treat new or recurrent brain tumors, including glioblastoma, medulloblastoma, astrocytoma, and metastatic brain tumors.

The CHMP’s opinion on Carmustine Obvius will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP’s recommendation, the commission will grant a centralized marketing authorization that will be valid in the European Union.

The EC typically makes a decision on a product within 67 days of the CHMP’s recommendation.

If approved, Carmustine Obvius will be available as a 100 mg powder and solvent for solution for infusion.

The active substance of Carmustine Obvius is carmustine, an alkylating antineoplastic agent of the nitrosourea type, which prevents DNA replication and transcription by alkylating reactive sites on nucleoproteins.

Carmustine Obvius is a generic of Carmubris, which has been authorized in the European Union since July 31, 1996.

Since Carmustine Obvius is administered intravenously and is 100% bioavailable, a bioequivalence study of the drug versus Carmubris was not required.

Carmustine Obvius is a product of Obvius Investment B.V.

Hodgkin lymphoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion of Carmustine Obvius, a generic version of Carmubris.

The CHMP is recommending marketing authorization for Carmustine Obvius as second-line treatment for Hodgkin and non-Hodgkin lymphoma as well as to treat new or recurrent brain tumors, including glioblastoma, medulloblastoma, astrocytoma, and metastatic brain tumors.

The CHMP’s opinion on Carmustine Obvius will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP’s recommendation, the commission will grant a centralized marketing authorization that will be valid in the European Union.

The EC typically makes a decision on a product within 67 days of the CHMP’s recommendation.

If approved, Carmustine Obvius will be available as a 100 mg powder and solvent for solution for infusion.

The active substance of Carmustine Obvius is carmustine, an alkylating antineoplastic agent of the nitrosourea type, which prevents DNA replication and transcription by alkylating reactive sites on nucleoproteins.

Carmustine Obvius is a generic of Carmubris, which has been authorized in the European Union since July 31, 1996.

Since Carmustine Obvius is administered intravenously and is 100% bioavailable, a bioequivalence study of the drug versus Carmubris was not required.

Carmustine Obvius is a product of Obvius Investment B.V.

Hodgkin lymphoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion of Carmustine Obvius, a generic version of Carmubris.

The CHMP is recommending marketing authorization for Carmustine Obvius as second-line treatment for Hodgkin and non-Hodgkin lymphoma as well as to treat new or recurrent brain tumors, including glioblastoma, medulloblastoma, astrocytoma, and metastatic brain tumors.

The CHMP’s opinion on Carmustine Obvius will be reviewed by the European Commission (EC).

If the EC agrees with the CHMP’s recommendation, the commission will grant a centralized marketing authorization that will be valid in the European Union.

The EC typically makes a decision on a product within 67 days of the CHMP’s recommendation.

If approved, Carmustine Obvius will be available as a 100 mg powder and solvent for solution for infusion.

The active substance of Carmustine Obvius is carmustine, an alkylating antineoplastic agent of the nitrosourea type, which prevents DNA replication and transcription by alkylating reactive sites on nucleoproteins.

Carmustine Obvius is a generic of Carmubris, which has been authorized in the European Union since July 31, 1996.

Since Carmustine Obvius is administered intravenously and is 100% bioavailable, a bioequivalence study of the drug versus Carmubris was not required.

Carmustine Obvius is a product of Obvius Investment B.V.