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Maintenance lenalidomide prolongs progression-free survival in DLBCL
Maintenance therapy with lenalidomide significantly prolongs progression-free survival (PFS) in elderly patients with diffuse large B-cell lymphoma (DLBCL), according to findings from a phase III trial.
None of the previous trials assessing a maintenance drug in this patient population – including bevacizumab, rituximab, enzastaurin, or everolimus – have reported such a benefit, Catherine Thieblemont, MD, PhD, of the department of hematology-oncology, Hôpital Saint-Louis, Paris, and her associates, reported.
The standard regimen for newly diagnosed DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but 30%-40% of patients have disease progression or relapse, usually during the first 2 years after diagnosis. Lenalidomide is an immunomodulator with antineoplastic activity and has shown activity in relapsed DLBCL. The investigators compared 24 months of lenalidomide maintenance therapy against a matching placebo in an international, randomized double-blind phase III trial involving 650 patients aged 60-80 years who showed either partial or complete responses to first-line R-CHOP.
After a median follow-up of 39 months (range, 0-74 months), median PFS was not yet reached in the lenalidomide group and was estimated to be 58.9 months in the placebo group, for a hazard ratio of 0.708 favoring lenalidomide. This represents a statistically significant and clinically meaningful improvement in PFS, Dr. Thieblemont and her associates noted (J Clin Oncol. 2017 Apr 20. doi: 10.1200/JCO.2017.72.6984).
This survival benefit was consistent across all subgroups of patients. Most important, PFS was significantly prolonged regardless of whether patients had shown only a partial response or a complete response to R-CHOP, the investigators said.
The maintenance therapy did not appear to prolong overall survival, which was 87% for lenalidomide and 89% for placebo.
“We do not yet fully understand the basis for lack of an [overall survival] benefit despite the positive PFS data. Other than that, this is not due to excessive toxicity in the experimental arm,” they said. “We speculate the reason may be differences in the outcomes after progression or some other unrecognized reason.”
The study was sponsored by the Lymphoma Academic Research Organisation of France and Celgene. Dr. Thieblemont reported ties to Celgene, Bayer, AbbVie, Janssen, and Roche. Her associates reported ties to numerous industry sources.
Maintenance therapy with lenalidomide significantly prolongs progression-free survival (PFS) in elderly patients with diffuse large B-cell lymphoma (DLBCL), according to findings from a phase III trial.
None of the previous trials assessing a maintenance drug in this patient population – including bevacizumab, rituximab, enzastaurin, or everolimus – have reported such a benefit, Catherine Thieblemont, MD, PhD, of the department of hematology-oncology, Hôpital Saint-Louis, Paris, and her associates, reported.
The standard regimen for newly diagnosed DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but 30%-40% of patients have disease progression or relapse, usually during the first 2 years after diagnosis. Lenalidomide is an immunomodulator with antineoplastic activity and has shown activity in relapsed DLBCL. The investigators compared 24 months of lenalidomide maintenance therapy against a matching placebo in an international, randomized double-blind phase III trial involving 650 patients aged 60-80 years who showed either partial or complete responses to first-line R-CHOP.
After a median follow-up of 39 months (range, 0-74 months), median PFS was not yet reached in the lenalidomide group and was estimated to be 58.9 months in the placebo group, for a hazard ratio of 0.708 favoring lenalidomide. This represents a statistically significant and clinically meaningful improvement in PFS, Dr. Thieblemont and her associates noted (J Clin Oncol. 2017 Apr 20. doi: 10.1200/JCO.2017.72.6984).
This survival benefit was consistent across all subgroups of patients. Most important, PFS was significantly prolonged regardless of whether patients had shown only a partial response or a complete response to R-CHOP, the investigators said.
The maintenance therapy did not appear to prolong overall survival, which was 87% for lenalidomide and 89% for placebo.
“We do not yet fully understand the basis for lack of an [overall survival] benefit despite the positive PFS data. Other than that, this is not due to excessive toxicity in the experimental arm,” they said. “We speculate the reason may be differences in the outcomes after progression or some other unrecognized reason.”
The study was sponsored by the Lymphoma Academic Research Organisation of France and Celgene. Dr. Thieblemont reported ties to Celgene, Bayer, AbbVie, Janssen, and Roche. Her associates reported ties to numerous industry sources.
Maintenance therapy with lenalidomide significantly prolongs progression-free survival (PFS) in elderly patients with diffuse large B-cell lymphoma (DLBCL), according to findings from a phase III trial.
None of the previous trials assessing a maintenance drug in this patient population – including bevacizumab, rituximab, enzastaurin, or everolimus – have reported such a benefit, Catherine Thieblemont, MD, PhD, of the department of hematology-oncology, Hôpital Saint-Louis, Paris, and her associates, reported.
The standard regimen for newly diagnosed DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but 30%-40% of patients have disease progression or relapse, usually during the first 2 years after diagnosis. Lenalidomide is an immunomodulator with antineoplastic activity and has shown activity in relapsed DLBCL. The investigators compared 24 months of lenalidomide maintenance therapy against a matching placebo in an international, randomized double-blind phase III trial involving 650 patients aged 60-80 years who showed either partial or complete responses to first-line R-CHOP.
After a median follow-up of 39 months (range, 0-74 months), median PFS was not yet reached in the lenalidomide group and was estimated to be 58.9 months in the placebo group, for a hazard ratio of 0.708 favoring lenalidomide. This represents a statistically significant and clinically meaningful improvement in PFS, Dr. Thieblemont and her associates noted (J Clin Oncol. 2017 Apr 20. doi: 10.1200/JCO.2017.72.6984).
This survival benefit was consistent across all subgroups of patients. Most important, PFS was significantly prolonged regardless of whether patients had shown only a partial response or a complete response to R-CHOP, the investigators said.
The maintenance therapy did not appear to prolong overall survival, which was 87% for lenalidomide and 89% for placebo.
“We do not yet fully understand the basis for lack of an [overall survival] benefit despite the positive PFS data. Other than that, this is not due to excessive toxicity in the experimental arm,” they said. “We speculate the reason may be differences in the outcomes after progression or some other unrecognized reason.”
The study was sponsored by the Lymphoma Academic Research Organisation of France and Celgene. Dr. Thieblemont reported ties to Celgene, Bayer, AbbVie, Janssen, and Roche. Her associates reported ties to numerous industry sources.
Key clinical point:
Major finding: Median progression-free survival was not yet reached in the lenalidomide group and was estimated to be 58.9 months in the placebo group, for a hazard ratio of 0.708 favoring lenalidomide.
Data source: A 5-year international, randomized double-blind placebo-controlled phase III trial involving 650 patients aged 60-80 years.
Disclosures: The study was sponsored by the Lymphoma Academic Research Organisation of France and Celgene. Dr. Thieblemont reported ties to Celgene, Bayer, AbbVie, Janssen, and Roche. Her associates reported ties to numerous industry sources.
Pembrolizumab could change treatment paradigm, team says
The anti-PD-1 therapy pembrolizumab could change the treatment paradigm of relapsed or refractory classic Hodgkin lymphoma (cHL), according to researchers.
In a phase 2 trial, pembrolizumab produced an overall response rate (ORR) of 69% and a complete response (CR) rate of 22% in adults with cHL who had failed treatment with brentuximab vedotin (BV), autologous hematopoietic stem cell transplant (auto-HSCT), or both.
The researchers said the safety profile of pembrolizumab was “acceptable” and largely consistent with safety in previous studies of the drug.
Twelve percent of patients temporarily stopped taking pembrolizumab due to treatment-related adverse events (AEs), and 4% stopped taking the drug entirely as a result of AEs.
Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues reported these results, from the KEYNOTE-087 trial, in the Journal of Clinical Oncology.
The trial was sponsored by Merck, the company that markets pembrolizumab as Keytruda.
In KEYNOTE-087, the researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Efficacy
Across all 210 enrolled patients, the ORR was 69.0%, and the CR rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
For the entire study cohort, the median duration of response was not reached, and the median overall survival was not reached. At 9 months, the overall survival rate was 97.5%, and the progression-free survival rate was 63.4%.
Safety
The most common AEs related to pembrolizumab were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
Nine patients (4.3%) stopped taking pembrolizumab due to treatment-related AEs, including myocarditis, myelitis, myositis, pneumonitis, infusion-related reactions, and cytokine release syndrome.
Twenty-six patients (12.4%) had treatment interruptions due to pembrolizumab-related AEs.
Two patients died during follow-up, but neither death was considered related to pembrolizumab. One patient died of septic shock and the other of acute graft-versus-host disease. 
The anti-PD-1 therapy pembrolizumab could change the treatment paradigm of relapsed or refractory classic Hodgkin lymphoma (cHL), according to researchers.
In a phase 2 trial, pembrolizumab produced an overall response rate (ORR) of 69% and a complete response (CR) rate of 22% in adults with cHL who had failed treatment with brentuximab vedotin (BV), autologous hematopoietic stem cell transplant (auto-HSCT), or both.
The researchers said the safety profile of pembrolizumab was “acceptable” and largely consistent with safety in previous studies of the drug.
Twelve percent of patients temporarily stopped taking pembrolizumab due to treatment-related adverse events (AEs), and 4% stopped taking the drug entirely as a result of AEs.
Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues reported these results, from the KEYNOTE-087 trial, in the Journal of Clinical Oncology.
The trial was sponsored by Merck, the company that markets pembrolizumab as Keytruda.
In KEYNOTE-087, the researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Efficacy
Across all 210 enrolled patients, the ORR was 69.0%, and the CR rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
For the entire study cohort, the median duration of response was not reached, and the median overall survival was not reached. At 9 months, the overall survival rate was 97.5%, and the progression-free survival rate was 63.4%.
Safety
The most common AEs related to pembrolizumab were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
Nine patients (4.3%) stopped taking pembrolizumab due to treatment-related AEs, including myocarditis, myelitis, myositis, pneumonitis, infusion-related reactions, and cytokine release syndrome.
Twenty-six patients (12.4%) had treatment interruptions due to pembrolizumab-related AEs.
Two patients died during follow-up, but neither death was considered related to pembrolizumab. One patient died of septic shock and the other of acute graft-versus-host disease.
The anti-PD-1 therapy pembrolizumab could change the treatment paradigm of relapsed or refractory classic Hodgkin lymphoma (cHL), according to researchers.
In a phase 2 trial, pembrolizumab produced an overall response rate (ORR) of 69% and a complete response (CR) rate of 22% in adults with cHL who had failed treatment with brentuximab vedotin (BV), autologous hematopoietic stem cell transplant (auto-HSCT), or both.
The researchers said the safety profile of pembrolizumab was “acceptable” and largely consistent with safety in previous studies of the drug.
Twelve percent of patients temporarily stopped taking pembrolizumab due to treatment-related adverse events (AEs), and 4% stopped taking the drug entirely as a result of AEs.
Craig H. Moskowitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues reported these results, from the KEYNOTE-087 trial, in the Journal of Clinical Oncology.
The trial was sponsored by Merck, the company that markets pembrolizumab as Keytruda.
In KEYNOTE-087, the researchers evaluated pembrolizumab (a 200 mg fixed dose every 3 weeks) in patients with relapsed or refractory cHL across 3 cohorts:
Cohort 1: Patients who progressed after auto-HSCT and subsequent treatment with BV
Cohort 2: Patients who failed salvage chemotherapy, were ineligible for a transplant, and progressed after BV
Cohort 3: Patients who progressed after auto-HSCT and did not receive BV after transplant.
Efficacy
Across all 210 enrolled patients, the ORR was 69.0%, and the CR rate was 22.4%.
In Cohort 1 (n=69), the ORR was 73.9%. The CR rate was 21.7%, the partial response (PR) rate was 52.2%, 15.9% of patients had stable disease (SD), and 7.2% progressed. In 82.2% of responders, the response lasted 6 months or more.
In Cohort 2 (n=81), the ORR was 64.2%. The CR rate was 24.7%, the PR rate was 39.5%, 12.3% of patients had SD, and 21.0% progressed. In 70.0% of responders, the response lasted 6 months or more.
In Cohort 3 (n=60), the ORR was 70.0%. Twenty percent of patients had a CR, 50.0% had a PR, 16.7% had SD, and 13.3% progressed. In 75.6% of responders, the response lasted 6 months or more.
Results also included an analysis of patients with primary refractory disease (n=73), which was defined as failure to achieve CR or PR with first-line treatment. In this patient population, the ORR was 79.5%.
An ORR of 67.8% was reported in patients who relapsed after 3 or more lines of prior therapy (99/146).
For the entire study cohort, the median duration of response was not reached, and the median overall survival was not reached. At 9 months, the overall survival rate was 97.5%, and the progression-free survival rate was 63.4%.
Safety
The most common AEs related to pembrolizumab were hypothyroidism (12.4%), pyrexia (10.5%), fatigue (9.0%), rash (7.6%), diarrhea (7.1%), headache (6.2%), nausea (5.7%), cough (5.7%), and neutropenia (5.2%).
The most common grade 3/4 treatment-related AEs were neutropenia (2.4%), diarrhea (1.0%), and dyspnea (1.0%). Immune-mediated AEs included pneumonitis (2.9%), hyperthyroidism (2.9%), colitis (1.0%), and myositis (1.0%).
Nine patients (4.3%) stopped taking pembrolizumab due to treatment-related AEs, including myocarditis, myelitis, myositis, pneumonitis, infusion-related reactions, and cytokine release syndrome.
Twenty-six patients (12.4%) had treatment interruptions due to pembrolizumab-related AEs.
Two patients died during follow-up, but neither death was considered related to pembrolizumab. One patient died of septic shock and the other of acute graft-versus-host disease.
EMA recommends orphan status for drug for DLBCL
The European Medicines Agency (EMA) has recommended that PQR309 receive orphan drug designation for the treatment of patients with diffuse large B-cell lymphoma (DLBCL).
PQR309, is an oral, brain-penetrant, dual inhibitor of the PI3K/mTOR pathway being developed by PIQUR Therapeutics AG.
PQR309 is currently being investigated in phase 1 and 2 studies in relapsed or refractory lymphoma (NCT02249429), relapsed or refractory primary central nervous system lymphoma (NCT02669511), and other malignancies.
Preclinical research of PQR309 in lymphomas was presented at the AACR Annual Meeting 2017 (abstract 2652).
Researchers tested the drug in 40 cell lines—27 DLBCL, 10 mantle cell lymphoma, and 3 splenic marginal zone lymphoma.
The researchers reported that PQR309 had “potent antiproliferative activity” in most of the cell lines.
The median IC50 was 166 nM in DLBCL cell lines, 235 nM in mantle cell lymphoma cell lines, and 214 nM in splenic marginal zone lymphoma cell lines.
In addition, PQR309 demonstrated similar activity in activated B-cell like DLBCL and germinal center B-cell like DLBCL.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
The European Medicines Agency (EMA) has recommended that PQR309 receive orphan drug designation for the treatment of patients with diffuse large B-cell lymphoma (DLBCL).
PQR309, is an oral, brain-penetrant, dual inhibitor of the PI3K/mTOR pathway being developed by PIQUR Therapeutics AG.
PQR309 is currently being investigated in phase 1 and 2 studies in relapsed or refractory lymphoma (NCT02249429), relapsed or refractory primary central nervous system lymphoma (NCT02669511), and other malignancies.
Preclinical research of PQR309 in lymphomas was presented at the AACR Annual Meeting 2017 (abstract 2652).
Researchers tested the drug in 40 cell lines—27 DLBCL, 10 mantle cell lymphoma, and 3 splenic marginal zone lymphoma.
The researchers reported that PQR309 had “potent antiproliferative activity” in most of the cell lines.
The median IC50 was 166 nM in DLBCL cell lines, 235 nM in mantle cell lymphoma cell lines, and 214 nM in splenic marginal zone lymphoma cell lines.
In addition, PQR309 demonstrated similar activity in activated B-cell like DLBCL and germinal center B-cell like DLBCL.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
The European Medicines Agency (EMA) has recommended that PQR309 receive orphan drug designation for the treatment of patients with diffuse large B-cell lymphoma (DLBCL).
PQR309, is an oral, brain-penetrant, dual inhibitor of the PI3K/mTOR pathway being developed by PIQUR Therapeutics AG.
PQR309 is currently being investigated in phase 1 and 2 studies in relapsed or refractory lymphoma (NCT02249429), relapsed or refractory primary central nervous system lymphoma (NCT02669511), and other malignancies.
Preclinical research of PQR309 in lymphomas was presented at the AACR Annual Meeting 2017 (abstract 2652).
Researchers tested the drug in 40 cell lines—27 DLBCL, 10 mantle cell lymphoma, and 3 splenic marginal zone lymphoma.
The researchers reported that PQR309 had “potent antiproliferative activity” in most of the cell lines.
The median IC50 was 166 nM in DLBCL cell lines, 235 nM in mantle cell lymphoma cell lines, and 214 nM in splenic marginal zone lymphoma cell lines.
In addition, PQR309 demonstrated similar activity in activated B-cell like DLBCL and germinal center B-cell like DLBCL.
About orphan designation
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.
The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.
Fertility treatments linked to risk of pediatric cancers
Children born to mothers who underwent fertility treatments have an increased risk of developing pediatric neoplasms, according to research published in the American Journal of Obstetrics & Gynecology.
The study showed an increased risk of malignancies and benign tumors among children conceived after fertility treatments.
However, the risk of leukemias and lymphomas among these children was not significantly different from the risk among children who were conceived spontaneously.
The study was a population-based cohort analysis of babies born between 1991 and 2013 at Soroka University Medical Center in Beer-Sheva, Israel, with follow-up to age 18.
Of the 242,187 newborn infants in the study, 237,863 (98.3%) were conceived spontaneously, 2603 (1.1%) were conceived after in vitro fertilization (IVF), and 1721 (0.7%) were conceived after ovulation induction (OI) treatments.
During a median follow-up of 10.55 years, there were 1498 neoplasms reported, including 1074 benign tumors and 429 malignancies.
The rate of neoplasms per 10,000 children was 61.85 for the entire study cohort, 111.41 for the IVF group, 110.40 for the OI group, and 60.96 for the spontaneous conception group (P<0.001 for the comparison between spontaneous conception and both types of fertility treatments).
The rate of benign tumors per 10,000 children was 44.35 for the entire study cohort, 84.51 for the IVF group, 69.73 for the OI group, and 43.72 for the spontaneous conception group (P=0.002).
The rate of malignancies per 10,000 children was 17.71 for the entire study cohort, 26.89 for the IVF group, 40.67 for the OI group, and 17.44 for the spontaneous conception group (P=0.038).
The rate of leukemia per 10,000 children was 3.72 for the entire study cohort (n=90 leukemia cases total), 0 for the IVF group (n=0), 5.81 for the OI group (n=1), and 3.74 for the spontaneous conception group (n=89, P=0.56).
The rate of lymphoma per 10,000 children was 2.27 for the entire study cohort (n=55), 7.68 for the IVF group (n=2), 0 for the OI group (n=0), and 2.23 for the spontaneous conception group (n=53, P=0.15).
The researchers said the association between fertility treatments and total pediatric neoplasms or total malignancies remained significant in analyses controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age.
For any fertility treatment, the adjusted hazard ratio (aHR) for all neoplasms was 1.97, and the aHR for all malignancies was 1.96.
For IVF, the aHR was 2.48 for all neoplasms and 1.89 for all malignancies. For OI, the aHR was 1.51 for all neoplasms and 2.03 for all malignancies.
“The research concludes that the association between IVF and total pediatric neoplasms and malignancies is significant,” said study author Eyal Sheiner, MD, PhD, of Ben-Gurion University of the Negev in Beer-Sheva, Israel.
“With increasing numbers of offspring conceived after fertility treatments, it is important to follow up on their health.”
Children born to mothers who underwent fertility treatments have an increased risk of developing pediatric neoplasms, according to research published in the American Journal of Obstetrics & Gynecology.
The study showed an increased risk of malignancies and benign tumors among children conceived after fertility treatments.
However, the risk of leukemias and lymphomas among these children was not significantly different from the risk among children who were conceived spontaneously.
The study was a population-based cohort analysis of babies born between 1991 and 2013 at Soroka University Medical Center in Beer-Sheva, Israel, with follow-up to age 18.
Of the 242,187 newborn infants in the study, 237,863 (98.3%) were conceived spontaneously, 2603 (1.1%) were conceived after in vitro fertilization (IVF), and 1721 (0.7%) were conceived after ovulation induction (OI) treatments.
During a median follow-up of 10.55 years, there were 1498 neoplasms reported, including 1074 benign tumors and 429 malignancies.
The rate of neoplasms per 10,000 children was 61.85 for the entire study cohort, 111.41 for the IVF group, 110.40 for the OI group, and 60.96 for the spontaneous conception group (P<0.001 for the comparison between spontaneous conception and both types of fertility treatments).
The rate of benign tumors per 10,000 children was 44.35 for the entire study cohort, 84.51 for the IVF group, 69.73 for the OI group, and 43.72 for the spontaneous conception group (P=0.002).
The rate of malignancies per 10,000 children was 17.71 for the entire study cohort, 26.89 for the IVF group, 40.67 for the OI group, and 17.44 for the spontaneous conception group (P=0.038).
The rate of leukemia per 10,000 children was 3.72 for the entire study cohort (n=90 leukemia cases total), 0 for the IVF group (n=0), 5.81 for the OI group (n=1), and 3.74 for the spontaneous conception group (n=89, P=0.56).
The rate of lymphoma per 10,000 children was 2.27 for the entire study cohort (n=55), 7.68 for the IVF group (n=2), 0 for the OI group (n=0), and 2.23 for the spontaneous conception group (n=53, P=0.15).
The researchers said the association between fertility treatments and total pediatric neoplasms or total malignancies remained significant in analyses controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age.
For any fertility treatment, the adjusted hazard ratio (aHR) for all neoplasms was 1.97, and the aHR for all malignancies was 1.96.
For IVF, the aHR was 2.48 for all neoplasms and 1.89 for all malignancies. For OI, the aHR was 1.51 for all neoplasms and 2.03 for all malignancies.
“The research concludes that the association between IVF and total pediatric neoplasms and malignancies is significant,” said study author Eyal Sheiner, MD, PhD, of Ben-Gurion University of the Negev in Beer-Sheva, Israel.
“With increasing numbers of offspring conceived after fertility treatments, it is important to follow up on their health.”
Children born to mothers who underwent fertility treatments have an increased risk of developing pediatric neoplasms, according to research published in the American Journal of Obstetrics & Gynecology.
The study showed an increased risk of malignancies and benign tumors among children conceived after fertility treatments.
However, the risk of leukemias and lymphomas among these children was not significantly different from the risk among children who were conceived spontaneously.
The study was a population-based cohort analysis of babies born between 1991 and 2013 at Soroka University Medical Center in Beer-Sheva, Israel, with follow-up to age 18.
Of the 242,187 newborn infants in the study, 237,863 (98.3%) were conceived spontaneously, 2603 (1.1%) were conceived after in vitro fertilization (IVF), and 1721 (0.7%) were conceived after ovulation induction (OI) treatments.
During a median follow-up of 10.55 years, there were 1498 neoplasms reported, including 1074 benign tumors and 429 malignancies.
The rate of neoplasms per 10,000 children was 61.85 for the entire study cohort, 111.41 for the IVF group, 110.40 for the OI group, and 60.96 for the spontaneous conception group (P<0.001 for the comparison between spontaneous conception and both types of fertility treatments).
The rate of benign tumors per 10,000 children was 44.35 for the entire study cohort, 84.51 for the IVF group, 69.73 for the OI group, and 43.72 for the spontaneous conception group (P=0.002).
The rate of malignancies per 10,000 children was 17.71 for the entire study cohort, 26.89 for the IVF group, 40.67 for the OI group, and 17.44 for the spontaneous conception group (P=0.038).
The rate of leukemia per 10,000 children was 3.72 for the entire study cohort (n=90 leukemia cases total), 0 for the IVF group (n=0), 5.81 for the OI group (n=1), and 3.74 for the spontaneous conception group (n=89, P=0.56).
The rate of lymphoma per 10,000 children was 2.27 for the entire study cohort (n=55), 7.68 for the IVF group (n=2), 0 for the OI group (n=0), and 2.23 for the spontaneous conception group (n=53, P=0.15).
The researchers said the association between fertility treatments and total pediatric neoplasms or total malignancies remained significant in analyses controlled for confounders such as gestational diabetes mellitus, hypertensive disorders, preterm birth, and maternal age.
For any fertility treatment, the adjusted hazard ratio (aHR) for all neoplasms was 1.97, and the aHR for all malignancies was 1.96.
For IVF, the aHR was 2.48 for all neoplasms and 1.89 for all malignancies. For OI, the aHR was 1.51 for all neoplasms and 2.03 for all malignancies.
“The research concludes that the association between IVF and total pediatric neoplasms and malignancies is significant,” said study author Eyal Sheiner, MD, PhD, of Ben-Gurion University of the Negev in Beer-Sheva, Israel.
“With increasing numbers of offspring conceived after fertility treatments, it is important to follow up on their health.”
Program allows select Europeans access to belinostat
A managed access program is making the histone deacetylase inhibitor belinostat (Beleodaq®) available to patients in Europe who have relapsed or refractory peripheral T-cell lymphoma (PTCL).
The program allows physicians to request belinostat for individual PTCL patients who have no alternative treatment options.
This enables patients to use belinostat ahead of a potential European approval. There are currently no approved treatments for PTCL in Europe.
The program will provide access to belinostat for patients in the UK, Germany, France, Spain, Italy, Denmark, Sweden, Norway, Finland, Belgium, The Netherlands, Luxembourg, and Austria.
The managed access program was made possible via an agreement between Onxeo, the company developing belinostat, and Clinigen Group plc., a company focused on providing access to medicines.
Healthcare professionals can obtain details about the belinostat managed access program by calling a Clinigen representative at +44 (0) 1283 44 347 or emailing customer.services@clinigengroup.com.
A managed access program is making the histone deacetylase inhibitor belinostat (Beleodaq®) available to patients in Europe who have relapsed or refractory peripheral T-cell lymphoma (PTCL).
The program allows physicians to request belinostat for individual PTCL patients who have no alternative treatment options.
This enables patients to use belinostat ahead of a potential European approval. There are currently no approved treatments for PTCL in Europe.
The program will provide access to belinostat for patients in the UK, Germany, France, Spain, Italy, Denmark, Sweden, Norway, Finland, Belgium, The Netherlands, Luxembourg, and Austria.
The managed access program was made possible via an agreement between Onxeo, the company developing belinostat, and Clinigen Group plc., a company focused on providing access to medicines.
Healthcare professionals can obtain details about the belinostat managed access program by calling a Clinigen representative at +44 (0) 1283 44 347 or emailing customer.services@clinigengroup.com.
A managed access program is making the histone deacetylase inhibitor belinostat (Beleodaq®) available to patients in Europe who have relapsed or refractory peripheral T-cell lymphoma (PTCL).
The program allows physicians to request belinostat for individual PTCL patients who have no alternative treatment options.
This enables patients to use belinostat ahead of a potential European approval. There are currently no approved treatments for PTCL in Europe.
The program will provide access to belinostat for patients in the UK, Germany, France, Spain, Italy, Denmark, Sweden, Norway, Finland, Belgium, The Netherlands, Luxembourg, and Austria.
The managed access program was made possible via an agreement between Onxeo, the company developing belinostat, and Clinigen Group plc., a company focused on providing access to medicines.
Healthcare professionals can obtain details about the belinostat managed access program by calling a Clinigen representative at +44 (0) 1283 44 347 or emailing customer.services@clinigengroup.com.
Drug receives fast track designation for follicular lymphoma
The US Food and Drug Administration (FDA) has granted fast track designation to the EZH2 inhibitor tazemetostat as a treatment for relapsed or refractory follicular lymphoma, with or without EZH2-activating mutations.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review.
In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
Tazemetostat also has fast track designation from the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with EZH2-activating mutations.
Tazemetostat is under investigation as monotherapy and in combination with other agents as a treatment for multiple cancers.
Results from a phase 1 study suggested tazemetostat can produce durable responses in patients with advanced non-Hodgkin lymphomas, including follicular lymphoma and DLBCL. The study was presented at the 2015 ASH Annual Meeting.
Tazemetostat is currently under investigation in a phase 2 trial of adults with relapsed or refractory DLBCL or follicular lymphoma.
Interim efficacy and safety data from this study are scheduled to be presented at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, on June 14, 2017, at 2:00 pm CET.
Tazemetostat is being developed by Epizyme, Inc.
The US Food and Drug Administration (FDA) has granted fast track designation to the EZH2 inhibitor tazemetostat as a treatment for relapsed or refractory follicular lymphoma, with or without EZH2-activating mutations.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review.
In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
Tazemetostat also has fast track designation from the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with EZH2-activating mutations.
Tazemetostat is under investigation as monotherapy and in combination with other agents as a treatment for multiple cancers.
Results from a phase 1 study suggested tazemetostat can produce durable responses in patients with advanced non-Hodgkin lymphomas, including follicular lymphoma and DLBCL. The study was presented at the 2015 ASH Annual Meeting.
Tazemetostat is currently under investigation in a phase 2 trial of adults with relapsed or refractory DLBCL or follicular lymphoma.
Interim efficacy and safety data from this study are scheduled to be presented at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, on June 14, 2017, at 2:00 pm CET.
Tazemetostat is being developed by Epizyme, Inc.
The US Food and Drug Administration (FDA) has granted fast track designation to the EZH2 inhibitor tazemetostat as a treatment for relapsed or refractory follicular lymphoma, with or without EZH2-activating mutations.
The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review.
In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.
Tazemetostat also has fast track designation from the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) with EZH2-activating mutations.
Tazemetostat is under investigation as monotherapy and in combination with other agents as a treatment for multiple cancers.
Results from a phase 1 study suggested tazemetostat can produce durable responses in patients with advanced non-Hodgkin lymphomas, including follicular lymphoma and DLBCL. The study was presented at the 2015 ASH Annual Meeting.
Tazemetostat is currently under investigation in a phase 2 trial of adults with relapsed or refractory DLBCL or follicular lymphoma.
Interim efficacy and safety data from this study are scheduled to be presented at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, on June 14, 2017, at 2:00 pm CET.
Tazemetostat is being developed by Epizyme, Inc.
FDA issues warnings about illegal ‘anticancer’ products
The US Food and Drug Administration (FDA) has posted warning letters addressed to 14 US-based companies illegally selling more than 65 products.
The companies are fraudulently claiming that these products prevent, diagnose, treat, or cure cancer.
The products are being marketed and sold without FDA approval, most commonly on websites and social media platforms.
“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment,” said Douglas W. Stearn, director of the Office of Enforcement and Import Operations in the FDA’s Office of Regulatory Affairs.
“We encourage people to remain vigilant whether online or in a store, and avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult a healthcare professional about proper prevention, diagnosis, and treatment of cancer.”
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate, or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses.
The illegally sold products cited in the FDA’s warning letters include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostics (such as thermography devices).
They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing, or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anticancer claims.
The FDA has requested responses from the 14 companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure, injunction, and/or criminal prosecution.
As part of the FDA’s effort to protect consumers from cancer health fraud, the FDA has issued more than 90 warning letters in the past 10 years to companies marketing hundreds of fraudulent cancer-related products on websites, social media, and in stores.
Although many of these companies have stopped selling the products or making fraudulent claims, numerous unsafe and unapproved products continue to be sold directly to consumers due, in part, to the ease with which companies can move their marketing operations to new websites.
The FDA continues to monitor and take action against companies promoting and selling unproven treatments in an effort to minimize the potential dangers to consumers and to educate consumers about the risks.
The FDA encourages healthcare professionals and consumers to report adverse reactions associated with these or similar products to the FDA’s MedWatch program.
The US Food and Drug Administration (FDA) has posted warning letters addressed to 14 US-based companies illegally selling more than 65 products.
The companies are fraudulently claiming that these products prevent, diagnose, treat, or cure cancer.
The products are being marketed and sold without FDA approval, most commonly on websites and social media platforms.
“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment,” said Douglas W. Stearn, director of the Office of Enforcement and Import Operations in the FDA’s Office of Regulatory Affairs.
“We encourage people to remain vigilant whether online or in a store, and avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult a healthcare professional about proper prevention, diagnosis, and treatment of cancer.”
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate, or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses.
The illegally sold products cited in the FDA’s warning letters include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostics (such as thermography devices).
They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing, or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anticancer claims.
The FDA has requested responses from the 14 companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure, injunction, and/or criminal prosecution.
As part of the FDA’s effort to protect consumers from cancer health fraud, the FDA has issued more than 90 warning letters in the past 10 years to companies marketing hundreds of fraudulent cancer-related products on websites, social media, and in stores.
Although many of these companies have stopped selling the products or making fraudulent claims, numerous unsafe and unapproved products continue to be sold directly to consumers due, in part, to the ease with which companies can move their marketing operations to new websites.
The FDA continues to monitor and take action against companies promoting and selling unproven treatments in an effort to minimize the potential dangers to consumers and to educate consumers about the risks.
The FDA encourages healthcare professionals and consumers to report adverse reactions associated with these or similar products to the FDA’s MedWatch program.
The US Food and Drug Administration (FDA) has posted warning letters addressed to 14 US-based companies illegally selling more than 65 products.
The companies are fraudulently claiming that these products prevent, diagnose, treat, or cure cancer.
The products are being marketed and sold without FDA approval, most commonly on websites and social media platforms.
“Consumers should not use these or similar unproven products because they may be unsafe and could prevent a person from seeking an appropriate and potentially life-saving cancer diagnosis or treatment,” said Douglas W. Stearn, director of the Office of Enforcement and Import Operations in the FDA’s Office of Regulatory Affairs.
“We encourage people to remain vigilant whether online or in a store, and avoid purchasing products marketed to treat cancer without any proof they will work. Patients should consult a healthcare professional about proper prevention, diagnosis, and treatment of cancer.”
It is a violation of the Federal Food, Drug and Cosmetic Act to market and sell products that claim to prevent, diagnose, treat, mitigate, or cure diseases without first demonstrating to the FDA that they are safe and effective for their labeled uses.
The illegally sold products cited in the FDA’s warning letters include a variety of product types, such as pills, topical creams, ointments, oils, drops, syrups, teas, and diagnostics (such as thermography devices).
They include products marketed for use by humans or pets that make illegal, unproven claims regarding preventing, reversing, or curing cancer; killing/inhibiting cancer cells or tumors; or other similar anticancer claims.
The FDA has requested responses from the 14 companies stating how the violations will be corrected. Failure to correct the violations promptly may result in legal action, including product seizure, injunction, and/or criminal prosecution.
As part of the FDA’s effort to protect consumers from cancer health fraud, the FDA has issued more than 90 warning letters in the past 10 years to companies marketing hundreds of fraudulent cancer-related products on websites, social media, and in stores.
Although many of these companies have stopped selling the products or making fraudulent claims, numerous unsafe and unapproved products continue to be sold directly to consumers due, in part, to the ease with which companies can move their marketing operations to new websites.
The FDA continues to monitor and take action against companies promoting and selling unproven treatments in an effort to minimize the potential dangers to consumers and to educate consumers about the risks.
The FDA encourages healthcare professionals and consumers to report adverse reactions associated with these or similar products to the FDA’s MedWatch program.
A spouse’s cancer diagnosis can lower household income
A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.
Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.
“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.
“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”
One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.
“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”
“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”
The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.
The women had lower average employment rates, so the decrease represented a larger relative decline for them.
When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.
When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.
Total family income decreased by up to 4.8% among men and 8.5% among women.
The investigators found the declines were due to lower earnings among both cancer patients and their spouses.
“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”
“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”
Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.
“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”
A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.
Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.
“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.
“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”
One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.
“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”
“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”
The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.
The women had lower average employment rates, so the decrease represented a larger relative decline for them.
When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.
When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.
Total family income decreased by up to 4.8% among men and 8.5% among women.
The investigators found the declines were due to lower earnings among both cancer patients and their spouses.
“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”
“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”
Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.
“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”
A spouse’s cancer diagnosis can significantly diminish family income, according to research published in the Journal of Health Economics.
Investigators tracked changes in employment and income among working-age couples in Canada and found that, on average, a spousal cancer diagnosis results in a 5% decline in household income for men and a 9% decline for women.
“The average annual household income for the working-age couples we studied was about $100,000, so the loss of income per family is about $5000 to $9000, which is a pretty substantial decline,” said study author R. Vincent Pohl, PhD, of the University of Georgia in Athens, Georgia.
“In a situation where one household member has a devastating diagnosis, it leads to the whole household suffering economically.”
One reason for the income decline is attributed to what’s known as the caregiver effect—when one family member reduces his or her own employment to support another.
“We thought that the household’s lessened income could happen in one of two ways,” Dr Pohl said. “One is that the person who is diagnosed might not be able to work because they are getting treatment or they’re too sick to work.”
“The second is what happens to their spouse. Does the spouse work more to make up for the lost income or does the spouse also reduce his or her labor supply in order to take care of the spouse that is diagnosed with cancer? We find the latter, that spouses reduce their labor supply and therefore have lowered income levels, which leads to the household having lower income levels as well.”
The investigators found that, in the 5 years after a spouse’s cancer diagnosis, both husbands and wives reduced their employment rates by about 2.4 percentage points, on average.
The women had lower average employment rates, so the decrease represented a larger relative decline for them.
When a wife was diagnosed with cancer, her husband’s annual earnings decreased by about $2000, or 3.5% of his income.
When a husband was diagnosed with cancer, his wife’s annual earnings decreased by about $1500, or 6% of her income.
Total family income decreased by up to 4.8% among men and 8.5% among women.
The investigators found the declines were due to lower earnings among both cancer patients and their spouses.
“What we need to think about, in terms of policy implications, is how we can protect not just individuals from the consequences of getting sick, but their entire family,” Dr Pohl said. That’s not really something that existing policies do.”
“If you think about disability insurance, it’s a function of an individual’s inability to work. It doesn’t take into account that family members might have to take care of an individual and therefore might also lose their job or reduce their working hours and, thus, their income.”
Dr Pohl said this study allowed the investigators to examine behavior on a level that’s representative for the entire country of Canada, but the findings may not be transferable to the US, where healthcare is handled differently than in many developed nations.
“One reason why we don’t see that the spouse works more, potentially, is that health insurance is not provided through jobs in Canada,” Dr Pohl said. “In the United States, we could expect that if one spouse is diagnosed with a disease, the other spouse has to keep their job in order to keep health insurance for the family.”
In mantle cell lymphoma, triple therapy proves too toxic
Combined idelalisib, lenalidomide, and rituximab proved excessively toxic for the treatment of relapsed and refractory mantle cell and follicular lymphoma in two phase I trials conducted by the Alliance for Clinical Trials in Oncology.
The unexpected outcome, which led to early study termination, underscores the need for caution as new treatment combinations are proposed, Sonali M. Smith, MD, of the University of Chicago and her colleagues said in The Lancet Haematology.
In four of the first eight patients enrolled in the mantle cell lymphoma (A051201) and follicular lymphoma (A051202) phase I trials between July 9, 2013, and Sept. 30, 2014, unexpected dose-limiting toxicities occurred, including grade 4 sepsis syndrome, grade 4 hypotension with grade 3 rash and fevers, grade 4 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation with fevers, and grade 3 pulmonary infection with grade 3 maculopapular rash.
The adverse events occurred between 9 and 20 days after treatment initiation and coincided with rituximab infusions, the researchers said. No treatment-related deaths occurred (Lancet Haematol. 2017 Apr;4:e176-82).
Overall, 8 of 11 patients were removed from treatment because of an adverse event, and 3 of those required intensive care unit level of care.
Although rituximab was removed in both trials, two of the remaining three patients in the studies, including three with mantle cell lymphoma and eight with follicular lymphoma, experienced grade 3 rashes, and one had grade 3 AST elevations. In those with mantle cell lymphoma, the most common grade 3-4 adverse events were ALT elevations and rash. In those with follicular lymphoma, the most common grade 3-4 adverse events were neutropenia and rash.
“Given the inability to deliver treatment due to toxicity, both studies were permanently closed,” the researchers wrote, noting that the primary endpoint of safety and tolerability was not met.
The trials had the overall goal of developing targeted regimens to replace cytotoxic therapy.
“Both ... trials were designed to capitalize on the clinical synergy of lenalidomide and rituximab observed in previous trials by adding the highly specific PI3K delta inhibitor, idelalisib, for patients with relapsed mantle cell lymphoma and follicular lymphoma,” they said.
Previously available data implied that lenalidomide plus rituximab would be a safe backbone for therapy, and there was clinical rationale for adding idelalisib to that combination, they explained.
“Overall, our brief experience underscores the limited knowledge regarding drug interactions and off-target effects and serves as a cautionary note in developing biological agents in combination and against ad-hoc combinations outside of carefully monitored clinical trials,” they said.
The researchers noted that the nature of the toxicities observed in these trials supports an immune-activated state characterized by excessive inflammation.
“A more detailed assessment of effect on cytokines, T-cell subsets, natural killer cells, and clinical features predictive of toxicity and response should be included in any further testing of these classes of agents, and they should never be combined outside of a carefully designed and diligently monitored clinical trial setting,” they concluded.
The study was funded by the National Cancer Institute. Dr. Smith received research funding and consulting fees from Gilead and Celgene.
The findings by Dr. Smith and her colleagues add to several other reported studies that involved unexpected toxicities with various combinations of targeted agents in lymphoid malignancies.
Combinations of B-cell receptor signaling inhibitors can lead to immune dysregulation, which can be acute and severe when combined with immunomodulatory agents.
While the study of rational targeted combinations continues to hold immense potential in both untreated and relapsed/refractory disease, the combination must be thoroughly studied in the context of carefully and conservatively designed clinical trials.
Given the unpredictable nature of adverse events, the use of novel combinations outside of a clinical trial should be strongly discouraged.
Patrick M. Reagan, MD , and Paul M. Barr, MD , are with the James P. Wilmot Cancer Institute, University of Rochester, New York. Dr. Reagan reported having no disclosures. Dr. Barr has consulted for Gilead, Pharmacyclics, AbbVie, and Celgene. They made their remarks in an editorial that accompanied the article.
The findings by Dr. Smith and her colleagues add to several other reported studies that involved unexpected toxicities with various combinations of targeted agents in lymphoid malignancies.
Combinations of B-cell receptor signaling inhibitors can lead to immune dysregulation, which can be acute and severe when combined with immunomodulatory agents.
While the study of rational targeted combinations continues to hold immense potential in both untreated and relapsed/refractory disease, the combination must be thoroughly studied in the context of carefully and conservatively designed clinical trials.
Given the unpredictable nature of adverse events, the use of novel combinations outside of a clinical trial should be strongly discouraged.
Patrick M. Reagan, MD , and Paul M. Barr, MD , are with the James P. Wilmot Cancer Institute, University of Rochester, New York. Dr. Reagan reported having no disclosures. Dr. Barr has consulted for Gilead, Pharmacyclics, AbbVie, and Celgene. They made their remarks in an editorial that accompanied the article.
The findings by Dr. Smith and her colleagues add to several other reported studies that involved unexpected toxicities with various combinations of targeted agents in lymphoid malignancies.
Combinations of B-cell receptor signaling inhibitors can lead to immune dysregulation, which can be acute and severe when combined with immunomodulatory agents.
While the study of rational targeted combinations continues to hold immense potential in both untreated and relapsed/refractory disease, the combination must be thoroughly studied in the context of carefully and conservatively designed clinical trials.
Given the unpredictable nature of adverse events, the use of novel combinations outside of a clinical trial should be strongly discouraged.
Patrick M. Reagan, MD , and Paul M. Barr, MD , are with the James P. Wilmot Cancer Institute, University of Rochester, New York. Dr. Reagan reported having no disclosures. Dr. Barr has consulted for Gilead, Pharmacyclics, AbbVie, and Celgene. They made their remarks in an editorial that accompanied the article.
Combined idelalisib, lenalidomide, and rituximab proved excessively toxic for the treatment of relapsed and refractory mantle cell and follicular lymphoma in two phase I trials conducted by the Alliance for Clinical Trials in Oncology.
The unexpected outcome, which led to early study termination, underscores the need for caution as new treatment combinations are proposed, Sonali M. Smith, MD, of the University of Chicago and her colleagues said in The Lancet Haematology.
In four of the first eight patients enrolled in the mantle cell lymphoma (A051201) and follicular lymphoma (A051202) phase I trials between July 9, 2013, and Sept. 30, 2014, unexpected dose-limiting toxicities occurred, including grade 4 sepsis syndrome, grade 4 hypotension with grade 3 rash and fevers, grade 4 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation with fevers, and grade 3 pulmonary infection with grade 3 maculopapular rash.
The adverse events occurred between 9 and 20 days after treatment initiation and coincided with rituximab infusions, the researchers said. No treatment-related deaths occurred (Lancet Haematol. 2017 Apr;4:e176-82).
Overall, 8 of 11 patients were removed from treatment because of an adverse event, and 3 of those required intensive care unit level of care.
Although rituximab was removed in both trials, two of the remaining three patients in the studies, including three with mantle cell lymphoma and eight with follicular lymphoma, experienced grade 3 rashes, and one had grade 3 AST elevations. In those with mantle cell lymphoma, the most common grade 3-4 adverse events were ALT elevations and rash. In those with follicular lymphoma, the most common grade 3-4 adverse events were neutropenia and rash.
“Given the inability to deliver treatment due to toxicity, both studies were permanently closed,” the researchers wrote, noting that the primary endpoint of safety and tolerability was not met.
The trials had the overall goal of developing targeted regimens to replace cytotoxic therapy.
“Both ... trials were designed to capitalize on the clinical synergy of lenalidomide and rituximab observed in previous trials by adding the highly specific PI3K delta inhibitor, idelalisib, for patients with relapsed mantle cell lymphoma and follicular lymphoma,” they said.
Previously available data implied that lenalidomide plus rituximab would be a safe backbone for therapy, and there was clinical rationale for adding idelalisib to that combination, they explained.
“Overall, our brief experience underscores the limited knowledge regarding drug interactions and off-target effects and serves as a cautionary note in developing biological agents in combination and against ad-hoc combinations outside of carefully monitored clinical trials,” they said.
The researchers noted that the nature of the toxicities observed in these trials supports an immune-activated state characterized by excessive inflammation.
“A more detailed assessment of effect on cytokines, T-cell subsets, natural killer cells, and clinical features predictive of toxicity and response should be included in any further testing of these classes of agents, and they should never be combined outside of a carefully designed and diligently monitored clinical trial setting,” they concluded.
The study was funded by the National Cancer Institute. Dr. Smith received research funding and consulting fees from Gilead and Celgene.
Combined idelalisib, lenalidomide, and rituximab proved excessively toxic for the treatment of relapsed and refractory mantle cell and follicular lymphoma in two phase I trials conducted by the Alliance for Clinical Trials in Oncology.
The unexpected outcome, which led to early study termination, underscores the need for caution as new treatment combinations are proposed, Sonali M. Smith, MD, of the University of Chicago and her colleagues said in The Lancet Haematology.
In four of the first eight patients enrolled in the mantle cell lymphoma (A051201) and follicular lymphoma (A051202) phase I trials between July 9, 2013, and Sept. 30, 2014, unexpected dose-limiting toxicities occurred, including grade 4 sepsis syndrome, grade 4 hypotension with grade 3 rash and fevers, grade 4 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation with fevers, and grade 3 pulmonary infection with grade 3 maculopapular rash.
The adverse events occurred between 9 and 20 days after treatment initiation and coincided with rituximab infusions, the researchers said. No treatment-related deaths occurred (Lancet Haematol. 2017 Apr;4:e176-82).
Overall, 8 of 11 patients were removed from treatment because of an adverse event, and 3 of those required intensive care unit level of care.
Although rituximab was removed in both trials, two of the remaining three patients in the studies, including three with mantle cell lymphoma and eight with follicular lymphoma, experienced grade 3 rashes, and one had grade 3 AST elevations. In those with mantle cell lymphoma, the most common grade 3-4 adverse events were ALT elevations and rash. In those with follicular lymphoma, the most common grade 3-4 adverse events were neutropenia and rash.
“Given the inability to deliver treatment due to toxicity, both studies were permanently closed,” the researchers wrote, noting that the primary endpoint of safety and tolerability was not met.
The trials had the overall goal of developing targeted regimens to replace cytotoxic therapy.
“Both ... trials were designed to capitalize on the clinical synergy of lenalidomide and rituximab observed in previous trials by adding the highly specific PI3K delta inhibitor, idelalisib, for patients with relapsed mantle cell lymphoma and follicular lymphoma,” they said.
Previously available data implied that lenalidomide plus rituximab would be a safe backbone for therapy, and there was clinical rationale for adding idelalisib to that combination, they explained.
“Overall, our brief experience underscores the limited knowledge regarding drug interactions and off-target effects and serves as a cautionary note in developing biological agents in combination and against ad-hoc combinations outside of carefully monitored clinical trials,” they said.
The researchers noted that the nature of the toxicities observed in these trials supports an immune-activated state characterized by excessive inflammation.
“A more detailed assessment of effect on cytokines, T-cell subsets, natural killer cells, and clinical features predictive of toxicity and response should be included in any further testing of these classes of agents, and they should never be combined outside of a carefully designed and diligently monitored clinical trial setting,” they concluded.
The study was funded by the National Cancer Institute. Dr. Smith received research funding and consulting fees from Gilead and Celgene.
Key clinical point:
Major finding: Of 11 patients, 8 were removed from treatment because of an adverse event, and 3 of those required intensive care unit–level care.
Data source: Two phase I trials involving 11 patients.
Disclosures: The study was funded by the National Cancer Institute. Dr. Smith received research funding and consulting fees from Gilead and Celgene.
CHMP recommends approval for rituximab biosimilar
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for a biosimilar rituximab product called Rixathon.
The recommended authorization for Rixathon encompasses all the same indications as the reference medicine, MabThera, which includes non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).
The CHMP’s recommendation for Rixathon has been forwarded to the European Commission, which normally decides whether it will grant marketing authorization for a product within 67 days from the time the CHMP adopts its opinion.
The active substance of Rixathon is rituximab, a monoclonal antibody that binds specifically to the transmembrane protein CD20, which is found on both malignant and normal B cells.
In NHL and CLL, this promotes destruction of malignant B cells and controls tumor growth. In RA, GPA, and MPA, it reduces B cells involved in their pathogenesis.
The reference product for Rixathon is Mabthera, which was authorized for use in the European Union in June 1998.
The CHMP says studies have shown Rixathon to have comparable quality, safety, and efficacy to Mabthera.1, 2, 3
The applicant for Rixathon is Sandoz GmbH.
If authorized by the European Commission, Rixathon will be available for the following indications.
NHL
Rixathon is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV follicular lymphoma (FL).
Rixathon maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.
Rixathon monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.
Rixathon is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.
CLL
Rixathon in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory CLL.
The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.
RA, GPA, and MPA
Rixathon in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.
Rixathon in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.
1. Visser J et al. Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab. BioDrugs. 2013;27:495-507.
2. Da Silva A et al. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk Lymphoma. 2014;55:1609-1617.
3. Jurczak W et al. A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma. ASH Annual Meeting 2016.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for a biosimilar rituximab product called Rixathon.
The recommended authorization for Rixathon encompasses all the same indications as the reference medicine, MabThera, which includes non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).
The CHMP’s recommendation for Rixathon has been forwarded to the European Commission, which normally decides whether it will grant marketing authorization for a product within 67 days from the time the CHMP adopts its opinion.
The active substance of Rixathon is rituximab, a monoclonal antibody that binds specifically to the transmembrane protein CD20, which is found on both malignant and normal B cells.
In NHL and CLL, this promotes destruction of malignant B cells and controls tumor growth. In RA, GPA, and MPA, it reduces B cells involved in their pathogenesis.
The reference product for Rixathon is Mabthera, which was authorized for use in the European Union in June 1998.
The CHMP says studies have shown Rixathon to have comparable quality, safety, and efficacy to Mabthera.1, 2, 3
The applicant for Rixathon is Sandoz GmbH.
If authorized by the European Commission, Rixathon will be available for the following indications.
NHL
Rixathon is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV follicular lymphoma (FL).
Rixathon maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.
Rixathon monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.
Rixathon is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.
CLL
Rixathon in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory CLL.
The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.
RA, GPA, and MPA
Rixathon in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.
Rixathon in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.
1. Visser J et al. Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab. BioDrugs. 2013;27:495-507.
2. Da Silva A et al. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk Lymphoma. 2014;55:1609-1617.
3. Jurczak W et al. A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma. ASH Annual Meeting 2016.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for a biosimilar rituximab product called Rixathon.
The recommended authorization for Rixathon encompasses all the same indications as the reference medicine, MabThera, which includes non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).
The CHMP’s recommendation for Rixathon has been forwarded to the European Commission, which normally decides whether it will grant marketing authorization for a product within 67 days from the time the CHMP adopts its opinion.
The active substance of Rixathon is rituximab, a monoclonal antibody that binds specifically to the transmembrane protein CD20, which is found on both malignant and normal B cells.
In NHL and CLL, this promotes destruction of malignant B cells and controls tumor growth. In RA, GPA, and MPA, it reduces B cells involved in their pathogenesis.
The reference product for Rixathon is Mabthera, which was authorized for use in the European Union in June 1998.
The CHMP says studies have shown Rixathon to have comparable quality, safety, and efficacy to Mabthera.1, 2, 3
The applicant for Rixathon is Sandoz GmbH.
If authorized by the European Commission, Rixathon will be available for the following indications.
NHL
Rixathon is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV follicular lymphoma (FL).
Rixathon maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.
Rixathon monotherapy is indicated for the treatment of patients with stage III-IV FL who are chemo-resistant or are in their second or subsequent relapse after chemotherapy.
Rixathon is indicated for use in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) for the treatment of patients with CD20-positive diffuse large B-cell lymphoma.
CLL
Rixathon in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory CLL.
The CHMP noted that limited efficacy and safety data are available for patients previously treated with monoclonal antibodies, including rituximab, or patients who are refractory to previous rituximab plus chemotherapy.
RA, GPA, and MPA
Rixathon in combination with methotrexate is indicated for the treatment of adults with severe, active RA who have had an inadequate response to or cannot tolerate other disease-modifying anti-rheumatic drugs, including one or more tumor necrosis factor inhibitor therapies.
Rixathon in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.
1. Visser J et al. Physicochemical and Functional Comparability Between the Proposed Biosimilar Rituximab GP2013 and Originator Rituximab. BioDrugs. 2013;27:495-507.
2. Da Silva A et al. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk Lymphoma. 2014;55:1609-1617.
3. Jurczak W et al. A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma. ASH Annual Meeting 2016.