Lymphoma & Plasma Cell Disorders

Polyclonal immunoglobulin recovery 1 year after autologous stem cell transplantation (ASCT) in multiple myeloma patients may help to predict progression-free and overall survival, according to research published online Jan. 25 in Haematologica.

“Most multiple myeloma patients (85%-90%) exhibit immunoparesis at the time of diagnosis,” wrote Verónica González-Calle, MD, of the Instituto de Investigación Biomédica de Salamanca (Spain) and her coauthors. While the recovery of polyclonal immunoglobulins is expected after high doses of akylating agents like melphalan and the infusion of stem cells in the setting of ASCT, but whether the “persistence of immunoparesis after ASCT may predict worse progression or survival in patients with multiple myeloma” has not been studied.

In a retrospective cohort study, Dr. González-Calle and her colleagues evaluated 295 patients with symptomatic multiple myeloma who underwent ASCT at two referral centers in Spain.

One year after the transfer, 52% of the surviving 169 patients had experienced immunoglobulin recovery – defined as normalization of polyclonal immunoglobulin levels – and 48% had not (Haematologica. 2017 Jan 25. doi: 10.3324/haematol.2016.158345). Of the 88 patients who experienced immunoglobulin recovery, 36% had recovered by 100 days, 18% by 6 months, 17% by 9 months, and 26% by 1 year after stem cell transfer.

Immunoglobulin recovery significantly affected both progression-free survival (PFS) and overall survival. Median PFS was significantly longer in the 88 patients who experienced immunoglobulin recovery than in those who did not (60.4 vs. 27.9 months; hazard ratio, 0.45; 95% CI, 0.31-0.66; P less than .001). Similarly, median overall survival was 11.3 years in the group who experienced immunoglobulin recovery and 7.3 years in those with persistent immunoparesis from 1 year (P = .002).

There was also a significant interaction between the time to immunoglobulin recovery and the duration of PFS, with a shorter recovery time being associated with a significantly lower PFS.

“One possible explanation is that the prognostic significance of the polyclonal Ig recovery could be established only in those patients who lived enough to have experienced complete and uneventful B-cell reconstitution 1 year after ASCT,” the authors wrote. “Thus, if the polyclonal Igs have recovered by this time, our results would lead us to expect a positive outcome. By contrast, persistence of immunoparesis at this time was independently associated with shorter [progression-free survival] and worse [overall survival].”

The authors said polyclonal immunoglobulin recovery after 1 year could be considered an independent long-term marker for predicting PFS and overall survival. It is also a marker that could be easily assessed in clinical practice.

One author was supported by the Fundación AMIR and another was supported by the Fundación Española de Hematología y Hemoterapia and Janssen. No conflicts of interest were declared.

Polyclonal immunoglobulin recovery 1 year after autologous stem cell transplantation (ASCT) in multiple myeloma patients may help to predict progression-free and overall survival, according to research published online Jan. 25 in Haematologica.

“Most multiple myeloma patients (85%-90%) exhibit immunoparesis at the time of diagnosis,” wrote Verónica González-Calle, MD, of the Instituto de Investigación Biomédica de Salamanca (Spain) and her coauthors. While the recovery of polyclonal immunoglobulins is expected after high doses of akylating agents like melphalan and the infusion of stem cells in the setting of ASCT, but whether the “persistence of immunoparesis after ASCT may predict worse progression or survival in patients with multiple myeloma” has not been studied.

In a retrospective cohort study, Dr. González-Calle and her colleagues evaluated 295 patients with symptomatic multiple myeloma who underwent ASCT at two referral centers in Spain.

One year after the transfer, 52% of the surviving 169 patients had experienced immunoglobulin recovery – defined as normalization of polyclonal immunoglobulin levels – and 48% had not (Haematologica. 2017 Jan 25. doi: 10.3324/haematol.2016.158345). Of the 88 patients who experienced immunoglobulin recovery, 36% had recovered by 100 days, 18% by 6 months, 17% by 9 months, and 26% by 1 year after stem cell transfer.

Immunoglobulin recovery significantly affected both progression-free survival (PFS) and overall survival. Median PFS was significantly longer in the 88 patients who experienced immunoglobulin recovery than in those who did not (60.4 vs. 27.9 months; hazard ratio, 0.45; 95% CI, 0.31-0.66; P less than .001). Similarly, median overall survival was 11.3 years in the group who experienced immunoglobulin recovery and 7.3 years in those with persistent immunoparesis from 1 year (P = .002).

There was also a significant interaction between the time to immunoglobulin recovery and the duration of PFS, with a shorter recovery time being associated with a significantly lower PFS.

“One possible explanation is that the prognostic significance of the polyclonal Ig recovery could be established only in those patients who lived enough to have experienced complete and uneventful B-cell reconstitution 1 year after ASCT,” the authors wrote. “Thus, if the polyclonal Igs have recovered by this time, our results would lead us to expect a positive outcome. By contrast, persistence of immunoparesis at this time was independently associated with shorter [progression-free survival] and worse [overall survival].”

The authors said polyclonal immunoglobulin recovery after 1 year could be considered an independent long-term marker for predicting PFS and overall survival. It is also a marker that could be easily assessed in clinical practice.

One author was supported by the Fundación AMIR and another was supported by the Fundación Española de Hematología y Hemoterapia and Janssen. No conflicts of interest were declared.

Polyclonal immunoglobulin recovery 1 year after autologous stem cell transplantation (ASCT) in multiple myeloma patients may help to predict progression-free and overall survival, according to research published online Jan. 25 in Haematologica.

“Most multiple myeloma patients (85%-90%) exhibit immunoparesis at the time of diagnosis,” wrote Verónica González-Calle, MD, of the Instituto de Investigación Biomédica de Salamanca (Spain) and her coauthors. While the recovery of polyclonal immunoglobulins is expected after high doses of akylating agents like melphalan and the infusion of stem cells in the setting of ASCT, but whether the “persistence of immunoparesis after ASCT may predict worse progression or survival in patients with multiple myeloma” has not been studied.

In a retrospective cohort study, Dr. González-Calle and her colleagues evaluated 295 patients with symptomatic multiple myeloma who underwent ASCT at two referral centers in Spain.

One year after the transfer, 52% of the surviving 169 patients had experienced immunoglobulin recovery – defined as normalization of polyclonal immunoglobulin levels – and 48% had not (Haematologica. 2017 Jan 25. doi: 10.3324/haematol.2016.158345). Of the 88 patients who experienced immunoglobulin recovery, 36% had recovered by 100 days, 18% by 6 months, 17% by 9 months, and 26% by 1 year after stem cell transfer.

Immunoglobulin recovery significantly affected both progression-free survival (PFS) and overall survival. Median PFS was significantly longer in the 88 patients who experienced immunoglobulin recovery than in those who did not (60.4 vs. 27.9 months; hazard ratio, 0.45; 95% CI, 0.31-0.66; P less than .001). Similarly, median overall survival was 11.3 years in the group who experienced immunoglobulin recovery and 7.3 years in those with persistent immunoparesis from 1 year (P = .002).

There was also a significant interaction between the time to immunoglobulin recovery and the duration of PFS, with a shorter recovery time being associated with a significantly lower PFS.

“One possible explanation is that the prognostic significance of the polyclonal Ig recovery could be established only in those patients who lived enough to have experienced complete and uneventful B-cell reconstitution 1 year after ASCT,” the authors wrote. “Thus, if the polyclonal Igs have recovered by this time, our results would lead us to expect a positive outcome. By contrast, persistence of immunoparesis at this time was independently associated with shorter [progression-free survival] and worse [overall survival].”

The authors said polyclonal immunoglobulin recovery after 1 year could be considered an independent long-term marker for predicting PFS and overall survival. It is also a marker that could be easily assessed in clinical practice.

One author was supported by the Fundación AMIR and another was supported by the Fundación Española de Hematología y Hemoterapia and Janssen. No conflicts of interest were declared.

ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.

During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZV_IN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.

Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.

They were randomized to receive a four-dose regimen of either ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.

Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.

Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.

The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.

The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.

Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.

“Now another approach to prevention of herpes zoster infection is vaccination,” he said.

The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZV_IN showed promise with respect to safety in earlier studies, which led to the current trial.

“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.

“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.

Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.

sworcester@frontlinemedcom.com

ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.

During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZV_IN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.

Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.

They were randomized to receive a four-dose regimen of either ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.

Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.

Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.

The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.

The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.

Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.

“Now another approach to prevention of herpes zoster infection is vaccination,” he said.

The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZV_IN showed promise with respect to safety in earlier studies, which led to the current trial.

“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.

“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.

Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.

sworcester@frontlinemedcom.com

ORLANDO – An inactivated varicella zoster virus vaccine currently in development for adult patients undergoing autologous hematopoietic stem cell transplantation is efficacious and well tolerated, according to findings from a randomized, placebo-controlled, phase III trial.

During the course of the 2 1/2-year pivotal multicenter trial, confirmed herpes zoster infections occurred in 42 of 560 patients who were randomized to receive inactivated varicella zoster virus vaccine (ZV_IN) consistency lot (overall incidence of 32.8 cases/1,000 patient-years), compared with 113 of 564 patients who received placebo (overall incidence of 91.8/1,000 patient-years). The estimated vaccine efficacy was 63.8% after adjusting for age and duration of antiviral prophylaxis, Drew J. Winston, MD, reported at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The vaccine also was effective for reducing moderate and severe herpes zoster pain (estimated vaccine efficacy, 69.5%), for preventing postherpetic neuralgia (estimated vaccine efficacy, 83.7%), and for prevention of herpes zoster–related complications (estimated vaccine efficacy, 73.5%), he noted.

Study subjects were adults aged 18 years or older who were undergoing autologous hematopoietic stem cell transplantation (auto-HCT) for a malignancy or other indication. The most common underlying diseases were lymphoma and multiple myeloma. All patients had a history of varicella infection or were seropositive for varicella zoster virus (VZV) antibody, and had no history of VZV vaccine or herpes zoster infection within the prior year.

They were randomized to receive a four-dose regimen of either ZV_IN consistency lot, ZV_IN high-antigen lot, or placebo. A group of 106 patients who received the ZV_IN high-antigen lot were included in the safety analysis only. The first ZV_IN dose was administered about a month before transplantation, and doses two through four were administered about 30, 60, and 90 days after transplantation. About 90% in each group received antiviral agents after transplantation, and the duration of the use of antivirals also was similar in the groups. All patients were followed for the duration of the study, and those who developed herpes zoster were followed for 6 months after onset.

Herpes zoster cases were confirmed by polymerase chain reaction or by blinded endpoint committee adjudication.

Serious adverse events and vaccine-related serious adverse events occurred in a similar proportion of patients in the treatment and placebo groups (32.9% and 32.7%, and 0.8% and 0.9%, respectively). Vaccine-related events were primarily injection-site reactions. Systemic adverse events that occurred up to 28 days after vaccination were mainly gastrointestinal side effects, such as diarrhea, nausea, and vomiting. Pyrexia, oral mucositis, thrombocytopenia, and febrile neutropenia also were reported.

The most common serious adverse events were infectious complications, such as febrile neutropenia and relapse of underlying disease.

The findings are notable, as patients undergoing auto-HCT have an increased risk of developing herpes zoster infection and its complications, including postherpetic neuralgia, secondary bacterial infections, and disseminated VZV infection, as well as an increased risk of hospitalization and mortality, Dr. Winston explained.

Herpes zoster infections are associated primarily with cell-mediated immunity, and in older studies done prior to the routine use of antiviral prophylaxis, the reported incidence in auto-HCT patients was between 16% and 25%. Because of this high risk, current guidelines call for antiviral prophylaxis during auto-HCT, but even in this current era of acyclovir or valacyclovir prophylaxis, infections occur at relatively high rates after auto-HCT, he noted.

“Now another approach to prevention of herpes zoster infection is vaccination,” he said.

The live attenuated vaccine currently on the market is generally contraindicated in immunocompromised patients – at least in early period after transplantation, but ZV_IN showed promise with respect to safety in earlier studies, which led to the current trial.

“This study demonstrated that the inactivated varicella vaccine is very effective for preventing herpes zoster after autologous stem cell transplantation,” Dr. Winston said, noting that efficacy was observed both in those younger than age 50 years and in those aged 50 and older, and also in those who received prophylaxis for less than 3 months and for 3-6 months.

“Finally!” said one audience member, who noted during a discussion of the findings that there has long been a need for a vaccine to prevent herpes zoster in auto-HCT patients.

Dr. Winston reported receiving research funding from Oxford, and serving as a consultant to Merck and Chimerix.

sworcester@frontlinemedcom.com

New guidelines recommend proactively screening for the late-term effects of both myeloma itself and the multiple therapies many patients receive.

“We are entering a watershed period in which patients are expecting to live in excess of 5 to 10 years after a diagnosis of myeloma, and issues of survivorship are becoming increasingly important,” wrote John A. Snowden, MD, of Sheffield (England) Teaching Hospitals NHS Foundation Trust and his associates on behalf of the UK Myeloma Forum and the British Society for Haematology.

Late effects of myeloma and therapies “constitute a unique syndrome,” the guideline authors emphasized. “Survivorship in myeloma therefore requires specialized screening, coordinated management and multidisciplinary care” (Br J Haematol. 2017 Jan 20. doi: 10.1111/bjh.14514).

Hung Kuo Chun/Thinkstock

About half of myeloma patients have renal impairment and should undergo routine tests of serum calcium, parathyroid hormone, and vitamin D, the authors stated. Moderate to severe renal impairment, renal-related hyperparathyroidism, and nephrotic syndrome merit specialty referrals, they added. They also advised carefully managing diabetes and hypertension to delay end-stage kidney disease, modifying doses of lenalidomide and bisphosphonate doses in renally impaired patients, avoiding nephrotoxic drugs when possible, and considering erythropoiesis-stimulating agents and iron supplementation for anemia.

Endocrine disorders are also common in myeloma, and the authors recommended annual screening for hypothyroidism, hypogonadism in males, and menopausal symptoms in younger females, especially after HSCT. They emphasized annual measurements of weight, height, body mass index, waist circumference, strength and frailty, blood pressure, HbA_1c, and serum lipids, with referral to primary care when needed. For bone loss, they emphasized weight-bearing exercise, bisphosphonates, dietary changes, and calcium and vitamin D supplementation. They recommended specialist input on hormone therapy, if indicated.

Spinal cord or nerve-root compression often accompanies myeloma, and long-term survivors also may have peripheral neuropathy secondary to chemotherapy and other drug treatments, the guidelines noted. They recommended testing thyroid function and vitamin B₁₂ levels, reducing or eliminating neurotoxic agents, offering gabapentin or pregabalin for symptom control, and referring patients to pain specialists and neurologists for peripheral neuropathy beyond grade I. They also advised annual ophthalmic screening because even intermittent high-dose corticosteroid therapy can lead to cataracts.

Cardiopulmonary abnormalities affect about half of myeloma patients and deserve heightened attention, the authors stressed. They recommended routinely screening cardiovascular risk factors, testing natriuretic peptide annually, and performing electrocardiograms, echocardiography, and pulmonary function tests in at-risk patients. They also advised diet, weight control, smoking cessation, physical activity, and specialist referral for patients with established cardiovascular or pulmonary disease.

Bisphosphonates can cause osteonecrosis of the jaw, and chemotherapy and other therapies can cause oral dryness. The guidelines emphasized – in addition to monitoring for these adverse outcomes – the importance of oral hygiene, artificial saliva rinses, annual dental exams, and specialty evaluations for nonhealing lesions.

Novel myeloma therapies often cause diarrhea, but chronic diarrhea should be evaluated by a gastroenterologist to rule out malignancies, underlying bowel disease, AL amyloidosis, and bile acid malabsorption, the authors stressed. They also recommended annual assessments of liver function tests, drug and alcohol history, and vitamin D, B₁₂, folate, and ferritin levels. Nutritionists should provide input if patients are losing weight, they added.

Myeloma confers at least eight times the risk of myelodysplastic syndrome and acute myeloid leukemia, compared with the general population, the guidelines noted. Second primary malignancies can result from long-term exposure to lenalidomide and to such alkylating agents as melphalan. They advised considering myelodysplastic syndrome and acute myeloid leukemia in patients with persistent or worsening cytopenias, investigating symptoms that could indicate other malignancies, participating in cancer screening registries, and developing formal surveillance for second primary malignancies.

Additional recommendations included baseline geriatric assessment in elderly and frail patients; holistic assessments at the start of each line of treatment to pinpoint needs and concerns and to plan support services; and regular assessments of mood, anxiety, and cognitive status, with referrals for therapy, psychiatry, and support groups as needed. The authors also stressed the role of routine holistic needs-assessments to detect and track both pain and fatigue. Therapy should always include prehabilitation and rehabilitation, and clinicians should recommend ongoing regular physical activity and a healthy lifestyle, they emphasized.

To develop the guidelines, the experts searched Medline and the Cochrane databases for literature published between 2006 and March 31, 2016. They based key recommendations on evidence from randomized, controlled trials. When those data were not available, they resorted to other studies and to consensus expert opinion. The recommendations take cost-effectiveness into account, but are not based on formal health economic assessments, the experts noted.

Myeloma UK paid for an independent medical writer to help search the literature and draft the manuscript. Dr. Snowden also disclosed support from Sheffield Hospitals Charity.

New guidelines recommend proactively screening for the late-term effects of both myeloma itself and the multiple therapies many patients receive.

“We are entering a watershed period in which patients are expecting to live in excess of 5 to 10 years after a diagnosis of myeloma, and issues of survivorship are becoming increasingly important,” wrote John A. Snowden, MD, of Sheffield (England) Teaching Hospitals NHS Foundation Trust and his associates on behalf of the UK Myeloma Forum and the British Society for Haematology.

Late effects of myeloma and therapies “constitute a unique syndrome,” the guideline authors emphasized. “Survivorship in myeloma therefore requires specialized screening, coordinated management and multidisciplinary care” (Br J Haematol. 2017 Jan 20. doi: 10.1111/bjh.14514).

Hung Kuo Chun/Thinkstock

About half of myeloma patients have renal impairment and should undergo routine tests of serum calcium, parathyroid hormone, and vitamin D, the authors stated. Moderate to severe renal impairment, renal-related hyperparathyroidism, and nephrotic syndrome merit specialty referrals, they added. They also advised carefully managing diabetes and hypertension to delay end-stage kidney disease, modifying doses of lenalidomide and bisphosphonate doses in renally impaired patients, avoiding nephrotoxic drugs when possible, and considering erythropoiesis-stimulating agents and iron supplementation for anemia.

Endocrine disorders are also common in myeloma, and the authors recommended annual screening for hypothyroidism, hypogonadism in males, and menopausal symptoms in younger females, especially after HSCT. They emphasized annual measurements of weight, height, body mass index, waist circumference, strength and frailty, blood pressure, HbA_1c, and serum lipids, with referral to primary care when needed. For bone loss, they emphasized weight-bearing exercise, bisphosphonates, dietary changes, and calcium and vitamin D supplementation. They recommended specialist input on hormone therapy, if indicated.

Spinal cord or nerve-root compression often accompanies myeloma, and long-term survivors also may have peripheral neuropathy secondary to chemotherapy and other drug treatments, the guidelines noted. They recommended testing thyroid function and vitamin B₁₂ levels, reducing or eliminating neurotoxic agents, offering gabapentin or pregabalin for symptom control, and referring patients to pain specialists and neurologists for peripheral neuropathy beyond grade I. They also advised annual ophthalmic screening because even intermittent high-dose corticosteroid therapy can lead to cataracts.

Cardiopulmonary abnormalities affect about half of myeloma patients and deserve heightened attention, the authors stressed. They recommended routinely screening cardiovascular risk factors, testing natriuretic peptide annually, and performing electrocardiograms, echocardiography, and pulmonary function tests in at-risk patients. They also advised diet, weight control, smoking cessation, physical activity, and specialist referral for patients with established cardiovascular or pulmonary disease.

Bisphosphonates can cause osteonecrosis of the jaw, and chemotherapy and other therapies can cause oral dryness. The guidelines emphasized – in addition to monitoring for these adverse outcomes – the importance of oral hygiene, artificial saliva rinses, annual dental exams, and specialty evaluations for nonhealing lesions.

Novel myeloma therapies often cause diarrhea, but chronic diarrhea should be evaluated by a gastroenterologist to rule out malignancies, underlying bowel disease, AL amyloidosis, and bile acid malabsorption, the authors stressed. They also recommended annual assessments of liver function tests, drug and alcohol history, and vitamin D, B₁₂, folate, and ferritin levels. Nutritionists should provide input if patients are losing weight, they added.

Myeloma confers at least eight times the risk of myelodysplastic syndrome and acute myeloid leukemia, compared with the general population, the guidelines noted. Second primary malignancies can result from long-term exposure to lenalidomide and to such alkylating agents as melphalan. They advised considering myelodysplastic syndrome and acute myeloid leukemia in patients with persistent or worsening cytopenias, investigating symptoms that could indicate other malignancies, participating in cancer screening registries, and developing formal surveillance for second primary malignancies.

Additional recommendations included baseline geriatric assessment in elderly and frail patients; holistic assessments at the start of each line of treatment to pinpoint needs and concerns and to plan support services; and regular assessments of mood, anxiety, and cognitive status, with referrals for therapy, psychiatry, and support groups as needed. The authors also stressed the role of routine holistic needs-assessments to detect and track both pain and fatigue. Therapy should always include prehabilitation and rehabilitation, and clinicians should recommend ongoing regular physical activity and a healthy lifestyle, they emphasized.

To develop the guidelines, the experts searched Medline and the Cochrane databases for literature published between 2006 and March 31, 2016. They based key recommendations on evidence from randomized, controlled trials. When those data were not available, they resorted to other studies and to consensus expert opinion. The recommendations take cost-effectiveness into account, but are not based on formal health economic assessments, the experts noted.

Myeloma UK paid for an independent medical writer to help search the literature and draft the manuscript. Dr. Snowden also disclosed support from Sheffield Hospitals Charity.

New guidelines recommend proactively screening for the late-term effects of both myeloma itself and the multiple therapies many patients receive.

“We are entering a watershed period in which patients are expecting to live in excess of 5 to 10 years after a diagnosis of myeloma, and issues of survivorship are becoming increasingly important,” wrote John A. Snowden, MD, of Sheffield (England) Teaching Hospitals NHS Foundation Trust and his associates on behalf of the UK Myeloma Forum and the British Society for Haematology.

Late effects of myeloma and therapies “constitute a unique syndrome,” the guideline authors emphasized. “Survivorship in myeloma therefore requires specialized screening, coordinated management and multidisciplinary care” (Br J Haematol. 2017 Jan 20. doi: 10.1111/bjh.14514).

Hung Kuo Chun/Thinkstock

About half of myeloma patients have renal impairment and should undergo routine tests of serum calcium, parathyroid hormone, and vitamin D, the authors stated. Moderate to severe renal impairment, renal-related hyperparathyroidism, and nephrotic syndrome merit specialty referrals, they added. They also advised carefully managing diabetes and hypertension to delay end-stage kidney disease, modifying doses of lenalidomide and bisphosphonate doses in renally impaired patients, avoiding nephrotoxic drugs when possible, and considering erythropoiesis-stimulating agents and iron supplementation for anemia.

Endocrine disorders are also common in myeloma, and the authors recommended annual screening for hypothyroidism, hypogonadism in males, and menopausal symptoms in younger females, especially after HSCT. They emphasized annual measurements of weight, height, body mass index, waist circumference, strength and frailty, blood pressure, HbA_1c, and serum lipids, with referral to primary care when needed. For bone loss, they emphasized weight-bearing exercise, bisphosphonates, dietary changes, and calcium and vitamin D supplementation. They recommended specialist input on hormone therapy, if indicated.

Spinal cord or nerve-root compression often accompanies myeloma, and long-term survivors also may have peripheral neuropathy secondary to chemotherapy and other drug treatments, the guidelines noted. They recommended testing thyroid function and vitamin B₁₂ levels, reducing or eliminating neurotoxic agents, offering gabapentin or pregabalin for symptom control, and referring patients to pain specialists and neurologists for peripheral neuropathy beyond grade I. They also advised annual ophthalmic screening because even intermittent high-dose corticosteroid therapy can lead to cataracts.

Cardiopulmonary abnormalities affect about half of myeloma patients and deserve heightened attention, the authors stressed. They recommended routinely screening cardiovascular risk factors, testing natriuretic peptide annually, and performing electrocardiograms, echocardiography, and pulmonary function tests in at-risk patients. They also advised diet, weight control, smoking cessation, physical activity, and specialist referral for patients with established cardiovascular or pulmonary disease.

Bisphosphonates can cause osteonecrosis of the jaw, and chemotherapy and other therapies can cause oral dryness. The guidelines emphasized – in addition to monitoring for these adverse outcomes – the importance of oral hygiene, artificial saliva rinses, annual dental exams, and specialty evaluations for nonhealing lesions.

Novel myeloma therapies often cause diarrhea, but chronic diarrhea should be evaluated by a gastroenterologist to rule out malignancies, underlying bowel disease, AL amyloidosis, and bile acid malabsorption, the authors stressed. They also recommended annual assessments of liver function tests, drug and alcohol history, and vitamin D, B₁₂, folate, and ferritin levels. Nutritionists should provide input if patients are losing weight, they added.

Myeloma confers at least eight times the risk of myelodysplastic syndrome and acute myeloid leukemia, compared with the general population, the guidelines noted. Second primary malignancies can result from long-term exposure to lenalidomide and to such alkylating agents as melphalan. They advised considering myelodysplastic syndrome and acute myeloid leukemia in patients with persistent or worsening cytopenias, investigating symptoms that could indicate other malignancies, participating in cancer screening registries, and developing formal surveillance for second primary malignancies.

Additional recommendations included baseline geriatric assessment in elderly and frail patients; holistic assessments at the start of each line of treatment to pinpoint needs and concerns and to plan support services; and regular assessments of mood, anxiety, and cognitive status, with referrals for therapy, psychiatry, and support groups as needed. The authors also stressed the role of routine holistic needs-assessments to detect and track both pain and fatigue. Therapy should always include prehabilitation and rehabilitation, and clinicians should recommend ongoing regular physical activity and a healthy lifestyle, they emphasized.

To develop the guidelines, the experts searched Medline and the Cochrane databases for literature published between 2006 and March 31, 2016. They based key recommendations on evidence from randomized, controlled trials. When those data were not available, they resorted to other studies and to consensus expert opinion. The recommendations take cost-effectiveness into account, but are not based on formal health economic assessments, the experts noted.

Myeloma UK paid for an independent medical writer to help search the literature and draft the manuscript. Dr. Snowden also disclosed support from Sheffield Hospitals Charity.

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

For patients with newly diagnosed mantle cell lymphoma, duration and quality of response were superior with a regimen of bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) when compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), based on a post hoc analysis of the randomized, phase III LYM-3002 trial.

The difference was especially evident among patients who had a low- or medium-risk mantle cell lymphoma international prognostic index, Gregor Verhoef, MD, of University Hospital Leuven (Belgium) and his associates wrote in Haematologica.

In LYM-3002, 487 patients with newly diagnosed stage II-IV mantle cell lymphoma received six to eight 21-day cycles of intravenous VR-CAP or R-CHOP. Although overall response rates were similar for both groups, VR-CAP was associated with better duration of response and progression-free survival (PFS) and extended time to next treatment. To further explore these differences, the post hoc analysis stratified outcomes by response categories and analyzed depth of response based on computed tomography (CT) scans. Patients had a median age of about 65 years, and most were white males with stage-IV disease at diagnosis and an Eastern Cooperative Oncology Group performance status of 1 (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.152496).The superiority of VR-CAP held up across response categories. Complete responders to VR-CAP had more than twice the median PFS as did complete responders to R-CHOP (40.9 vs. 19.8 months; hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; P = .004). Among partial responders, median PFS was 17.1 vs. 11.7 months, respectively (HR, 0.62; 95% CI, 0.43-0.89; P = .01). Respective median duration of overall response was 42.1 months for VR-CAP vs. 18.5 months among complete responders (HR, 0.42; P less than .001), and 20.2 vs. 9.6 months among partial responders (HR, 0.57; P = .006).

Median time to next treatment also favored VR-CAP over R-CHOP among both complete responders (not evaluable vs. 26.6 months; HR, 0.42; P less than .001) and partial responders (35.3 vs. 24.3 months; HR, 0.57; P = .006), the researchers said. Further, CT scans showed that proportionally more patients in each response category became lesion-negative on VR-CAP than on R-CHOP. Among complete responders, rates of lesion negativity were 72% and 59%, respectively. Among partial responders, rates were 48% and 28%.

The effects of VR-CAP were most evident among patients with a low or medium-risk mantle cell lymphoma international prognostic index. Perhaps high-risk status signifies more rapidly proliferative disease, which negates the deeper responses with VR-CAP, compared with R-CHOP, they added.

The LYM-3002 study was supported by Janssen Research & Development and Millennium Pharmaceuticals. Dr. Verhoef had no disclosures. Nine coinvestigators disclosed ties to Janssen, Roche, GlaxoSmithKline, and several other pharmaceutical companies.

For patients with newly diagnosed mantle cell lymphoma, duration and quality of response were superior with a regimen of bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) when compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), based on a post hoc analysis of the randomized, phase III LYM-3002 trial.

The difference was especially evident among patients who had a low- or medium-risk mantle cell lymphoma international prognostic index, Gregor Verhoef, MD, of University Hospital Leuven (Belgium) and his associates wrote in Haematologica.

In LYM-3002, 487 patients with newly diagnosed stage II-IV mantle cell lymphoma received six to eight 21-day cycles of intravenous VR-CAP or R-CHOP. Although overall response rates were similar for both groups, VR-CAP was associated with better duration of response and progression-free survival (PFS) and extended time to next treatment. To further explore these differences, the post hoc analysis stratified outcomes by response categories and analyzed depth of response based on computed tomography (CT) scans. Patients had a median age of about 65 years, and most were white males with stage-IV disease at diagnosis and an Eastern Cooperative Oncology Group performance status of 1 (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.152496).The superiority of VR-CAP held up across response categories. Complete responders to VR-CAP had more than twice the median PFS as did complete responders to R-CHOP (40.9 vs. 19.8 months; hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; P = .004). Among partial responders, median PFS was 17.1 vs. 11.7 months, respectively (HR, 0.62; 95% CI, 0.43-0.89; P = .01). Respective median duration of overall response was 42.1 months for VR-CAP vs. 18.5 months among complete responders (HR, 0.42; P less than .001), and 20.2 vs. 9.6 months among partial responders (HR, 0.57; P = .006).

Median time to next treatment also favored VR-CAP over R-CHOP among both complete responders (not evaluable vs. 26.6 months; HR, 0.42; P less than .001) and partial responders (35.3 vs. 24.3 months; HR, 0.57; P = .006), the researchers said. Further, CT scans showed that proportionally more patients in each response category became lesion-negative on VR-CAP than on R-CHOP. Among complete responders, rates of lesion negativity were 72% and 59%, respectively. Among partial responders, rates were 48% and 28%.

The effects of VR-CAP were most evident among patients with a low or medium-risk mantle cell lymphoma international prognostic index. Perhaps high-risk status signifies more rapidly proliferative disease, which negates the deeper responses with VR-CAP, compared with R-CHOP, they added.

The LYM-3002 study was supported by Janssen Research & Development and Millennium Pharmaceuticals. Dr. Verhoef had no disclosures. Nine coinvestigators disclosed ties to Janssen, Roche, GlaxoSmithKline, and several other pharmaceutical companies.

For patients with newly diagnosed mantle cell lymphoma, duration and quality of response were superior with a regimen of bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) when compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), based on a post hoc analysis of the randomized, phase III LYM-3002 trial.

The difference was especially evident among patients who had a low- or medium-risk mantle cell lymphoma international prognostic index, Gregor Verhoef, MD, of University Hospital Leuven (Belgium) and his associates wrote in Haematologica.

In LYM-3002, 487 patients with newly diagnosed stage II-IV mantle cell lymphoma received six to eight 21-day cycles of intravenous VR-CAP or R-CHOP. Although overall response rates were similar for both groups, VR-CAP was associated with better duration of response and progression-free survival (PFS) and extended time to next treatment. To further explore these differences, the post hoc analysis stratified outcomes by response categories and analyzed depth of response based on computed tomography (CT) scans. Patients had a median age of about 65 years, and most were white males with stage-IV disease at diagnosis and an Eastern Cooperative Oncology Group performance status of 1 (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.152496).The superiority of VR-CAP held up across response categories. Complete responders to VR-CAP had more than twice the median PFS as did complete responders to R-CHOP (40.9 vs. 19.8 months; hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; P = .004). Among partial responders, median PFS was 17.1 vs. 11.7 months, respectively (HR, 0.62; 95% CI, 0.43-0.89; P = .01). Respective median duration of overall response was 42.1 months for VR-CAP vs. 18.5 months among complete responders (HR, 0.42; P less than .001), and 20.2 vs. 9.6 months among partial responders (HR, 0.57; P = .006).

Median time to next treatment also favored VR-CAP over R-CHOP among both complete responders (not evaluable vs. 26.6 months; HR, 0.42; P less than .001) and partial responders (35.3 vs. 24.3 months; HR, 0.57; P = .006), the researchers said. Further, CT scans showed that proportionally more patients in each response category became lesion-negative on VR-CAP than on R-CHOP. Among complete responders, rates of lesion negativity were 72% and 59%, respectively. Among partial responders, rates were 48% and 28%.

The effects of VR-CAP were most evident among patients with a low or medium-risk mantle cell lymphoma international prognostic index. Perhaps high-risk status signifies more rapidly proliferative disease, which negates the deeper responses with VR-CAP, compared with R-CHOP, they added.

The LYM-3002 study was supported by Janssen Research & Development and Millennium Pharmaceuticals. Dr. Verhoef had no disclosures. Nine coinvestigators disclosed ties to Janssen, Roche, GlaxoSmithKline, and several other pharmaceutical companies.

Photo by Etan J. Tal

New research has revealed factors that may increase the risk of B-cell non-Hodgkin lymphoma (B-NHL) in Israelis and Palestinians.

This large-scale, epidemiological study indicated that each group had its own unique risk factors.

However, in both groups, recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a hematopoietic malignancy were all associated with B-NHL.

A team of Palestinian and Israeli researchers reported these findings in PLOS ONE.

The researchers noted that Israelis and Palestinians share the same ecosystem but differ in terms of lifestyle, health behaviors, and medical systems. Yet both populations report high incidences of NHL.

To gain some insight into this phenomenon, the team conducted a study examining risk factors for B-NHL and its subtypes in these two populations.

The researchers looked at medical history, environmental factors, and lifestyle factors in 823 B-NHL patients and 808 healthy controls.

There were 516 Israeli Jews with B-NHL and 307 Palestinian Arabs with B-NHL. The mean age at diagnosis was 60 and 51, respectively.

The proportion of patients with diffuse large B-cell lymphoma was 71% of Palestinian Arabs and 41% of Israeli Jews. The proportion of patients with follicular lymphoma was 14% and 28%, respectively. And the proportion of patients with marginal zone lymphoma was 2% and 14%, respectively.

Using data from questionnaires, pathology review, serology, and genotyping, the researchers uncovered potential risk factors for B-NHL common to both populations and other factors unique to each population.

Results

The data showed that, in both Palestinian Arabs and Israeli Jews, B-NHL was associated with:

• Recreational sun exposure (odds ratio [OR]=1.4)
• Black hair-dye use (OR=1.70)
• A history of hospitalization for infection (OR=1.68)
• Having a first-degree relative with a hematopoietic malignancy (OR=1.69).

Smoking was associated with follicular lymphoma in both populations (OR=1.46). And greater-than-monthly indoor pesticide use was associated with diffuse large B-cell lymphoma in both populations (OR=2.01).

There was an inverse association between alcohol use and B-NHL for both populations (OR=0.46).

Among Palestinian Arabs only, risk factors for B-NHL included gardening (OR=1.93) and a history of herpes (OR=3.73), mononucleosis (OR=6.34), rubella (OR=2.86), and blood transfusion (OR=2.53).

Risk factors that applied to Israeli Jews only included growing fruits and vegetables (OR=1.87) and self-reported autoimmune diseases (OR=1.99).

The researchers said differences in risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by B-NHL subtypes suggest specific causal factors for different types of disease. However, these findings require further investigation to reveal their mechanisms.

“Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions,” said study author Ora Paltiel, of Hadassah-Hebrew University Medical Organization in Jerusalem, Israel.

“The study provided opportunities for training Palestinian and Israeli researchers and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations.” 

Photo by Etan J. Tal

New research has revealed factors that may increase the risk of B-cell non-Hodgkin lymphoma (B-NHL) in Israelis and Palestinians.

This large-scale, epidemiological study indicated that each group had its own unique risk factors.

However, in both groups, recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a hematopoietic malignancy were all associated with B-NHL.

A team of Palestinian and Israeli researchers reported these findings in PLOS ONE.

The researchers noted that Israelis and Palestinians share the same ecosystem but differ in terms of lifestyle, health behaviors, and medical systems. Yet both populations report high incidences of NHL.

To gain some insight into this phenomenon, the team conducted a study examining risk factors for B-NHL and its subtypes in these two populations.

The researchers looked at medical history, environmental factors, and lifestyle factors in 823 B-NHL patients and 808 healthy controls.

There were 516 Israeli Jews with B-NHL and 307 Palestinian Arabs with B-NHL. The mean age at diagnosis was 60 and 51, respectively.

The proportion of patients with diffuse large B-cell lymphoma was 71% of Palestinian Arabs and 41% of Israeli Jews. The proportion of patients with follicular lymphoma was 14% and 28%, respectively. And the proportion of patients with marginal zone lymphoma was 2% and 14%, respectively.

Using data from questionnaires, pathology review, serology, and genotyping, the researchers uncovered potential risk factors for B-NHL common to both populations and other factors unique to each population.

Results

The data showed that, in both Palestinian Arabs and Israeli Jews, B-NHL was associated with:

• Recreational sun exposure (odds ratio [OR]=1.4)
• Black hair-dye use (OR=1.70)
• A history of hospitalization for infection (OR=1.68)
• Having a first-degree relative with a hematopoietic malignancy (OR=1.69).

Smoking was associated with follicular lymphoma in both populations (OR=1.46). And greater-than-monthly indoor pesticide use was associated with diffuse large B-cell lymphoma in both populations (OR=2.01).

There was an inverse association between alcohol use and B-NHL for both populations (OR=0.46).

Among Palestinian Arabs only, risk factors for B-NHL included gardening (OR=1.93) and a history of herpes (OR=3.73), mononucleosis (OR=6.34), rubella (OR=2.86), and blood transfusion (OR=2.53).

Risk factors that applied to Israeli Jews only included growing fruits and vegetables (OR=1.87) and self-reported autoimmune diseases (OR=1.99).

The researchers said differences in risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by B-NHL subtypes suggest specific causal factors for different types of disease. However, these findings require further investigation to reveal their mechanisms.

“Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions,” said study author Ora Paltiel, of Hadassah-Hebrew University Medical Organization in Jerusalem, Israel.

“The study provided opportunities for training Palestinian and Israeli researchers and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations.” 

Photo by Etan J. Tal

New research has revealed factors that may increase the risk of B-cell non-Hodgkin lymphoma (B-NHL) in Israelis and Palestinians.

This large-scale, epidemiological study indicated that each group had its own unique risk factors.

However, in both groups, recreational sun exposure, black hair-dye use, a history of hospitalization for infection, and having a first-degree relative with a hematopoietic malignancy were all associated with B-NHL.

A team of Palestinian and Israeli researchers reported these findings in PLOS ONE.

The researchers noted that Israelis and Palestinians share the same ecosystem but differ in terms of lifestyle, health behaviors, and medical systems. Yet both populations report high incidences of NHL.

To gain some insight into this phenomenon, the team conducted a study examining risk factors for B-NHL and its subtypes in these two populations.

The researchers looked at medical history, environmental factors, and lifestyle factors in 823 B-NHL patients and 808 healthy controls.

There were 516 Israeli Jews with B-NHL and 307 Palestinian Arabs with B-NHL. The mean age at diagnosis was 60 and 51, respectively.

The proportion of patients with diffuse large B-cell lymphoma was 71% of Palestinian Arabs and 41% of Israeli Jews. The proportion of patients with follicular lymphoma was 14% and 28%, respectively. And the proportion of patients with marginal zone lymphoma was 2% and 14%, respectively.

Using data from questionnaires, pathology review, serology, and genotyping, the researchers uncovered potential risk factors for B-NHL common to both populations and other factors unique to each population.

Results

The data showed that, in both Palestinian Arabs and Israeli Jews, B-NHL was associated with:

• Recreational sun exposure (odds ratio [OR]=1.4)
• Black hair-dye use (OR=1.70)
• A history of hospitalization for infection (OR=1.68)
• Having a first-degree relative with a hematopoietic malignancy (OR=1.69).

Smoking was associated with follicular lymphoma in both populations (OR=1.46). And greater-than-monthly indoor pesticide use was associated with diffuse large B-cell lymphoma in both populations (OR=2.01).

There was an inverse association between alcohol use and B-NHL for both populations (OR=0.46).

Among Palestinian Arabs only, risk factors for B-NHL included gardening (OR=1.93) and a history of herpes (OR=3.73), mononucleosis (OR=6.34), rubella (OR=2.86), and blood transfusion (OR=2.53).

Risk factors that applied to Israeli Jews only included growing fruits and vegetables (OR=1.87) and self-reported autoimmune diseases (OR=1.99).

The researchers said differences in risk factors by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by B-NHL subtypes suggest specific causal factors for different types of disease. However, these findings require further investigation to reveal their mechanisms.

“Apart from the scientific contribution that this research provides in terms of understanding risk factors for NHL, the study entails an important research cooperation among many institutions,” said study author Ora Paltiel, of Hadassah-Hebrew University Medical Organization in Jerusalem, Israel.

“The study provided opportunities for training Palestinian and Israeli researchers and will provide for intellectual interaction for years to come. The data collected will also provide a research platform for the future study of lymphoma. Epidemiologic research has the potential to improve and preserve human health, and it can also serve as a bridge to dialogue among nations.” 

Follicular lymphoma

The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.

This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.

The approval is based on data submitted to the European Medicines Agency.

The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).

Therefore, the European Commission approved Truxima for the following indications.

Non-Hodgkin lymphoma 

Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.

Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Truxima 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.

Truxima 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.

Chronic lymphocytic leukemia

Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.

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 

Truxima 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.

Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

Truxima studies

There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).

Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).

Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).  

Follicular lymphoma

The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.

This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.

The approval is based on data submitted to the European Medicines Agency.

The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).

Therefore, the European Commission approved Truxima for the following indications.

Non-Hodgkin lymphoma 

Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.

Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Truxima 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.

Truxima 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.

Chronic lymphocytic leukemia

Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.

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 

Truxima 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.

Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

Truxima studies

There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).

Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).

Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).  

Follicular lymphoma

The European Commission has approved a biosimilar rituximab product, Truxima™, for all the same indications as the reference product, MabThera.

This means Truxima (formerly called CT-P10) is approved for use in the European Union to treat patients with non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA).

Truxima, a product of Celltrion Healthcare Hungary Kft, is the first biosimilar monoclonal antibody approved in an oncology indication worldwide.

The approval is based on data submitted to the European Medicines Agency.

The agency’s Committee for Medicinal Products for Human Use (CHMP) said the evidence suggests Truxima and MabThera are similar in terms of efficacy, safety, immunogenicity, pharmacodynamics, and pharmacokinetics in patients with RA and advanced follicular lymphoma (FL).

Therefore, the European Commission approved Truxima for the following indications.

Non-Hodgkin lymphoma 

Truxima is indicated for use in combination with chemotherapy to treat previously untreated patients with stage III-IV FL.

Truxima maintenance therapy is indicated for the treatment of FL patients responding to induction therapy.

Truxima 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.

Truxima 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.

Chronic lymphocytic leukemia

Truxima in combination with chemotherapy is indicated for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukemia.

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 

Truxima 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.

Truxima in combination with glucocorticoids is indicated for the induction of remission in adults with severe, active GPA or MPA.

Truxima studies

There are 3 ongoing, phase 3 trials of Truxima in patients with RA (NCT02149121), advanced FL (NCT02162771), and low-tumor-burden FL (NCT02260804).

Results from the phase 1/3 trial in patients with newly diagnosed, advanced FL suggest that Truxima and the reference rituximab are similar with regard to pharmacokinetics, immunogenicity, and safety (B Coiffier et al. ASH 2016, abstract 1807).

Results from the phase 3 study of RA patients indicate that Truxima is similar to reference products (EU and US-sourced rituximab) with regard to pharmacodynamics, safety, and efficacy for up to 24 weeks (DH Yoo et al. 2016 ACR/ARHP Annual Meeting, abstract 1635).  

The Food and Drug Administration has approved the use of lenalidomide (Revlimid) for maintenance therapy following autologous hematopoietic stem cell transplant in patients with multiple myeloma.

The expanded indication, announced Feb. 22, makes the immunomodulatory agent the first and only approved treatment for post autologous hematopoietic stem cell transplant (auto-HSCT) maintenance. It was initially approved in 2006 for use in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy, and that indication was expanded in 2015 to include those with newly diagnosed multiple myeloma.

According to Celgene, the maker of Revlimid, the latest approval was based on data showing that lenalidomide maintenance therapy delays disease progression following auto-HSCT. Updated phase III randomized controlled trial data from two studies including more than 1,000 patients demonstrated median progression-free survival (PFS) advantages with lenalidomide maintenance vs. no maintenance. In one study – the U.S.-based CALGB 1001014 – median PFS was 5.7 vs. 1.9 years for a difference of 3.8 years (hazard ratio, 0.38). In the second study – the European IFM 2005-02 – median PFS was 3.9 vs. 2 years, for a difference of 1.9 years (HR, 0.53).

sworcester@frontlinemedcom.com

The Food and Drug Administration has approved the use of lenalidomide (Revlimid) for maintenance therapy following autologous hematopoietic stem cell transplant in patients with multiple myeloma.

The expanded indication, announced Feb. 22, makes the immunomodulatory agent the first and only approved treatment for post autologous hematopoietic stem cell transplant (auto-HSCT) maintenance. It was initially approved in 2006 for use in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy, and that indication was expanded in 2015 to include those with newly diagnosed multiple myeloma.

According to Celgene, the maker of Revlimid, the latest approval was based on data showing that lenalidomide maintenance therapy delays disease progression following auto-HSCT. Updated phase III randomized controlled trial data from two studies including more than 1,000 patients demonstrated median progression-free survival (PFS) advantages with lenalidomide maintenance vs. no maintenance. In one study – the U.S.-based CALGB 1001014 – median PFS was 5.7 vs. 1.9 years for a difference of 3.8 years (hazard ratio, 0.38). In the second study – the European IFM 2005-02 – median PFS was 3.9 vs. 2 years, for a difference of 1.9 years (HR, 0.53).

sworcester@frontlinemedcom.com

The Food and Drug Administration has approved the use of lenalidomide (Revlimid) for maintenance therapy following autologous hematopoietic stem cell transplant in patients with multiple myeloma.

The expanded indication, announced Feb. 22, makes the immunomodulatory agent the first and only approved treatment for post autologous hematopoietic stem cell transplant (auto-HSCT) maintenance. It was initially approved in 2006 for use in combination with dexamethasone in patients with multiple myeloma who have received at least one prior therapy, and that indication was expanded in 2015 to include those with newly diagnosed multiple myeloma.

According to Celgene, the maker of Revlimid, the latest approval was based on data showing that lenalidomide maintenance therapy delays disease progression following auto-HSCT. Updated phase III randomized controlled trial data from two studies including more than 1,000 patients demonstrated median progression-free survival (PFS) advantages with lenalidomide maintenance vs. no maintenance. In one study – the U.S.-based CALGB 1001014 – median PFS was 5.7 vs. 1.9 years for a difference of 3.8 years (hazard ratio, 0.38). In the second study – the European IFM 2005-02 – median PFS was 3.9 vs. 2 years, for a difference of 1.9 years (HR, 0.53).

sworcester@frontlinemedcom.com

Photo courtesy of CDC

A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.

The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.

However, this was only true for non-elderly individuals.

There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.

Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.

The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.

The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.

Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).

“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.

On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.

The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.

The researchers said these results could be explained by uniform healthcare coverage through Medicare.

The team also said their findings may have significant policy implications.

“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.

“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”

Photo courtesy of CDC

A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.

The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.

However, this was only true for non-elderly individuals.

There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.

Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.

The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.

The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.

Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).

“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.

On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.

The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.

The researchers said these results could be explained by uniform healthcare coverage through Medicare.

The team also said their findings may have significant policy implications.

“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.

“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”

Photo courtesy of CDC

A new analysis indicates that cancer survivors may be more likely than the rest of the US population to change their prescription drug use due to financial concerns.

The study showed that cancer survivors were more likely to delay filling prescriptions, skip medication doses, request cheaper medications from their doctors, and engage in other cost-saving behaviors.

However, this was only true for non-elderly individuals.

There was no significant difference in cost-saving behaviors between elderly (age 65 and older) cancer survivors and elderly individuals in the general population.

Ahmedin Jemal, DVM, PhD, of the American Cancer Society in Atlanta, Georgia, and his colleagues reported these findings in Cancer.

The researchers used 2011-2014 data from the National Health Interview Survey, an annual household interview survey conducted by the US Centers for Disease Control and Prevention.

The survey included 8931 cancer survivors and 126,287 individuals without a cancer history.

Among non-elderly adults, 31.6% of those who had been diagnosed with cancer recently and 27.9% of those who had been diagnosed at least 2 years earlier reported a change in prescription drug use for financial reasons, compared with 21.4% of individuals without a history of cancer (P<0.05).

“Specifically, non-elderly cancer survivors were more likely to skip medication, delay filling a prescription, ask their doctor for lower-cost medication, and use alternative therapies for financial reasons compared with non-elderly individuals without a cancer history,” Dr Jemal said.

On the other hand, changes in prescription drug use for financial reasons were generally similar between elderly cancer survivors and elderly individuals without a cancer history.

The proportion of elderly individuals who changed their drug use for financial reasons was 24.9% among those who had been diagnosed with cancer recently, 21.8% among those who had been diagnosed at least 2 years earlier, and 20.4% among those without a history of cancer.

The researchers said these results could be explained by uniform healthcare coverage through Medicare.

The team also said their findings may have significant policy implications.

“Healthcare reforms addressing the financial burden of cancer among survivors, including the escalating cost of prescription drugs, should consider multiple comorbid conditions and high-deductible health plans, and the working poor,” Dr Jemal said.

“Our findings also have implications for doctor and patient communication about the financial burden of cancer when making treatment decisions, especially on the use of certain drugs that cost hundreds of thousands of dollars but with very small benefit compared with alternative and more affordable drugs.”

Benjamin Chaigne-Delalande

The US Food and Drug Administration (FDA) has granted fast track designation to CMD-003 (baltaleucel-T) for patients with relapsed/refractory lymphoma and post-transplant lymphoproliferative disease associated with Epstein-Barr virus (EBV).

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with EBV.

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About fast track designation

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 FDA’s 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 biologic license application or new drug 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.

CMD-003-related research

CMD-003 is currently under investigation in the phase 2 CITADEL trial for patients with extranodal natural killer T-cell lymphoma and the phase 2 CIVIC trial for patients with EBV-associated diffuse large B-cell lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology in 2014, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

Benjamin Chaigne-Delalande

The US Food and Drug Administration (FDA) has granted fast track designation to CMD-003 (baltaleucel-T) for patients with relapsed/refractory lymphoma and post-transplant lymphoproliferative disease associated with Epstein-Barr virus (EBV).

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with EBV.

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About fast track designation

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 FDA’s 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 biologic license application or new drug 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.

CMD-003-related research

CMD-003 is currently under investigation in the phase 2 CITADEL trial for patients with extranodal natural killer T-cell lymphoma and the phase 2 CIVIC trial for patients with EBV-associated diffuse large B-cell lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology in 2014, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.

Benjamin Chaigne-Delalande

The US Food and Drug Administration (FDA) has granted fast track designation to CMD-003 (baltaleucel-T) for patients with relapsed/refractory lymphoma and post-transplant lymphoproliferative disease associated with Epstein-Barr virus (EBV).

CMD-003 consists of patient-derived T cells that have been activated to kill malignant cells expressing antigens associated with EBV.

The T cells specifically target 4 EBV epitopes—LMP1, LMP2, EBNA, and BARF1.

CMD-003 is being developed by Cell Medica and the Baylor College of Medicine with funding provided, in part, by the Cancer Prevention and Research Institute of Texas.

About fast track designation

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 FDA’s 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 biologic license application or new drug 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.

CMD-003-related research

CMD-003 is currently under investigation in the phase 2 CITADEL trial for patients with extranodal natural killer T-cell lymphoma and the phase 2 CIVIC trial for patients with EBV-associated diffuse large B-cell lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disease.

Researchers have not published results from any trials of CMD-003, but they have published results with EBV-specific T-cell products related to CMD-003.

In one study, published in the Journal of Clinical Oncology in 2014, researchers administered cytotoxic T lymphocytes (CTLs) in 50 patients with EBV-associated Hodgkin or non-Hodgkin lymphoma.

Twenty-nine of the patients were in remission when they received CTL infusions, but they were at a high risk of relapse. The remaining 21 patients had relapsed or refractory disease at the time of CTL infusion.

Twenty-seven of the patients who received CTLs as an adjuvant treatment remained in remission at 3.1 years after treatment.

Their 2-year event-free survival rate was 82%. None of the patients died of lymphoma, but 9 died from complications associated with the chemotherapy and radiation they had received.

Of the 21 patients with relapsed or refractory disease, 13 responded to CTL infusions, and 11 patients achieved a complete response. In this group, the 2-year event-free survival rate was about 50%.

The researchers said there were no toxicities that were definitively related to CTL infusion.

One patient had central nervous system deterioration 2 weeks after infusion. This was attributed to disease progression but could possibly have been treatment-related.

Another patient developed respiratory complications about 4 weeks after a second CTL infusion that may have been treatment-related. However, the researchers attributed it to an intercurrent infection, and the patient made a complete recovery.