Multiple Myeloma

Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.

Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.

The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.

“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.

Racial and socioeconomic barriers should also be addressed, they added.

The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.

Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).

Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.

“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.

The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.

Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.

Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.

SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.

Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.

Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.

The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.

“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.

Racial and socioeconomic barriers should also be addressed, they added.

The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.

Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).

Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.

“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.

The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.

Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.

Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.

SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.

Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.

Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.

The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.

“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.

Racial and socioeconomic barriers should also be addressed, they added.

The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.

Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).

Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.

“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.

The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.

Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.

Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.

SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.

showing multiple myeloma

Targeted screening could potentially reduce the prevalence of multiple myeloma (MM), according to research published in JCO Clinical Cancer Informatics.

Researchers found that screening for monoclonal gammopathy of undetermined significance (MGUS) might reduce the risk of MM in individuals with a high lifetime risk of MGUS, which includes men, African Americans, and people with a family history of MM.

The researchers said patients who screen positive for MGUS could seek medical care early and try strategies such as aspirin, metformin, or weight reduction to potentially reduce their risk of progression from MGUS to MM.

However, additional studies are needed to confirm the effectiveness of aspirin, metformin, and weight-loss strategies in preventing MGUS progression.

“Screening for MGUS may have significant benefits by lowering the incidence of multiple myeloma, provided that effective and non-toxic interventions can be identified,” said study author Philipp Altrock, PhD, of Moffitt Cancer Center in Tampa, Florida.

Dr Altrock and his colleagues performed a series of computational modeling experiments to determine the best screening strategies in different groups of patients. The goal was to determine when screening should begin, how often it should occur, and in which individuals it could be most effective.

The researchers designed their model to predict the progression of MGUS to MM, the changes in MGUS and MM prevalence, and the annual follow-up mortality due to disease.

The team found evidence to suggest that screening strategies could reduce the risk of progression and the prevalence of MM. This effect was more pronounced in individuals who had a higher risk of MGUS.

Modeling suggested the prevalence of MM could be reduced by 19% in patients who begin screening at age 55 and have follow-up screening every 6 years.

A similar reduction in prevalence could also be achieved by starting screening at age 65 and following up every 2 years.

“Regular screening of MGUS candidates should start as early as possible, with biannual follow-up, and focus on high-risk individuals, especially with a family history of multiple myeloma or in groups with a strong indication of MGUS progression,” Dr Altrock said.

showing multiple myeloma

Targeted screening could potentially reduce the prevalence of multiple myeloma (MM), according to research published in JCO Clinical Cancer Informatics.

Researchers found that screening for monoclonal gammopathy of undetermined significance (MGUS) might reduce the risk of MM in individuals with a high lifetime risk of MGUS, which includes men, African Americans, and people with a family history of MM.

The researchers said patients who screen positive for MGUS could seek medical care early and try strategies such as aspirin, metformin, or weight reduction to potentially reduce their risk of progression from MGUS to MM.

However, additional studies are needed to confirm the effectiveness of aspirin, metformin, and weight-loss strategies in preventing MGUS progression.

“Screening for MGUS may have significant benefits by lowering the incidence of multiple myeloma, provided that effective and non-toxic interventions can be identified,” said study author Philipp Altrock, PhD, of Moffitt Cancer Center in Tampa, Florida.

Dr Altrock and his colleagues performed a series of computational modeling experiments to determine the best screening strategies in different groups of patients. The goal was to determine when screening should begin, how often it should occur, and in which individuals it could be most effective.

The researchers designed their model to predict the progression of MGUS to MM, the changes in MGUS and MM prevalence, and the annual follow-up mortality due to disease.

The team found evidence to suggest that screening strategies could reduce the risk of progression and the prevalence of MM. This effect was more pronounced in individuals who had a higher risk of MGUS.

Modeling suggested the prevalence of MM could be reduced by 19% in patients who begin screening at age 55 and have follow-up screening every 6 years.

A similar reduction in prevalence could also be achieved by starting screening at age 65 and following up every 2 years.

“Regular screening of MGUS candidates should start as early as possible, with biannual follow-up, and focus on high-risk individuals, especially with a family history of multiple myeloma or in groups with a strong indication of MGUS progression,” Dr Altrock said.

showing multiple myeloma

Targeted screening could potentially reduce the prevalence of multiple myeloma (MM), according to research published in JCO Clinical Cancer Informatics.

Researchers found that screening for monoclonal gammopathy of undetermined significance (MGUS) might reduce the risk of MM in individuals with a high lifetime risk of MGUS, which includes men, African Americans, and people with a family history of MM.

The researchers said patients who screen positive for MGUS could seek medical care early and try strategies such as aspirin, metformin, or weight reduction to potentially reduce their risk of progression from MGUS to MM.

However, additional studies are needed to confirm the effectiveness of aspirin, metformin, and weight-loss strategies in preventing MGUS progression.

“Screening for MGUS may have significant benefits by lowering the incidence of multiple myeloma, provided that effective and non-toxic interventions can be identified,” said study author Philipp Altrock, PhD, of Moffitt Cancer Center in Tampa, Florida.

Dr Altrock and his colleagues performed a series of computational modeling experiments to determine the best screening strategies in different groups of patients. The goal was to determine when screening should begin, how often it should occur, and in which individuals it could be most effective.

The researchers designed their model to predict the progression of MGUS to MM, the changes in MGUS and MM prevalence, and the annual follow-up mortality due to disease.

The team found evidence to suggest that screening strategies could reduce the risk of progression and the prevalence of MM. This effect was more pronounced in individuals who had a higher risk of MGUS.

Modeling suggested the prevalence of MM could be reduced by 19% in patients who begin screening at age 55 and have follow-up screening every 6 years.

A similar reduction in prevalence could also be achieved by starting screening at age 65 and following up every 2 years.

“Regular screening of MGUS candidates should start as early as possible, with biannual follow-up, and focus on high-risk individuals, especially with a family history of multiple myeloma or in groups with a strong indication of MGUS progression,” Dr Altrock said.

The European Commission has expanded the indication for denosumab (Xgeva), making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.

The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.

During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.

The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.

[email protected]

The European Commission has expanded the indication for denosumab (Xgeva), making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.

The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.

During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.

The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.

[email protected]

The European Commission has expanded the indication for denosumab (Xgeva), making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.

The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.

During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.

The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.

[email protected]

Photo by Bill Branson

The European Commission (EC) has approved an expanded indication for denosumab (Xgeva).

The drug is now approved for the prevention of skeletal-related events (SREs) in adults with advanced malignancies involving bone, which includes patients with multiple myeloma (MM).

Approval from the EC provides a centralized marketing authorization with unified labeling in all member countries of the European Union.

Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

Denosumab was previously approved by the EC to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.

Denosumab also received EC approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

The EC’s approval for denosumab in MM patients is based on data from the ’482 study, which were recently published in The Lancet Oncology.

In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.

Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859).

All patients also received investigators’ choice of first-line MM therapy.

The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P for non-inferiority=0.010).

There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.

But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.

Photo by Bill Branson

The European Commission (EC) has approved an expanded indication for denosumab (Xgeva).

The drug is now approved for the prevention of skeletal-related events (SREs) in adults with advanced malignancies involving bone, which includes patients with multiple myeloma (MM).

Approval from the EC provides a centralized marketing authorization with unified labeling in all member countries of the European Union.

Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

Denosumab was previously approved by the EC to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.

Denosumab also received EC approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

The EC’s approval for denosumab in MM patients is based on data from the ’482 study, which were recently published in The Lancet Oncology.

In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.

Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859).

All patients also received investigators’ choice of first-line MM therapy.

The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P for non-inferiority=0.010).

There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.

But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.

Photo by Bill Branson

The European Commission (EC) has approved an expanded indication for denosumab (Xgeva).

The drug is now approved for the prevention of skeletal-related events (SREs) in adults with advanced malignancies involving bone, which includes patients with multiple myeloma (MM).

Approval from the EC provides a centralized marketing authorization with unified labeling in all member countries of the European Union.

Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

Denosumab was previously approved by the EC to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.

Denosumab also received EC approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.

The EC’s approval for denosumab in MM patients is based on data from the ’482 study, which were recently published in The Lancet Oncology.

In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.

Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859).

All patients also received investigators’ choice of first-line MM therapy.

The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P for non-inferiority=0.010).

There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.

But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).

The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.

Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.

As it is in adults, fosaprepitant would be given to children as part of combination therapy.

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

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

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

Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.

Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.

Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).

The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.

Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.

As it is in adults, fosaprepitant would be given to children as part of combination therapy.

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

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

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

Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.

Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.

Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).

Photo by Bill Branson

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).

The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.

Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.

As it is in adults, fosaprepitant would be given to children as part of combination therapy.

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

If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.

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

Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.

Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.

Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).

Photo from PharmaMar

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).

PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.

Plitidepsin is intended to be used in combination with dexamethasone.

This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.

At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.

The CHMP’s review

Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.

The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.

The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.

Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).

Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.

Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.

The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.

PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.

About plitidepsin

Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.

Plitidepsin is currently in clinical development for hematologic malignancies.

In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.

In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.

Plitidepsin has received orphan drug designation in the European Union and the US.

Photo from PharmaMar

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).

PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.

Plitidepsin is intended to be used in combination with dexamethasone.

This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.

At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.

The CHMP’s review

Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.

The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.

The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.

Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).

Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.

Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.

The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.

PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.

About plitidepsin

Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.

Plitidepsin is currently in clinical development for hematologic malignancies.

In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.

In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.

Plitidepsin has received orphan drug designation in the European Union and the US.

Photo from PharmaMar

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended refusal of marketing authorization for plitidepsin (Aplidin).

PharmaMar is seeking approval for plitidepsin to treat adults with multiple myeloma (MM) who have received at least 3 prior treatments, including bortezomib and either lenalidomide or thalidomide.

Plitidepsin is intended to be used in combination with dexamethasone.

This is the second time the CHMP has recommended against authorizing plitidepsin for this indication. The first time was last December.

At that time, PharmaMar asked the CHMP to re-examine its opinion, and the CHMP obliged. The committee confirmed its negative opinion of plitidepsin last week.

The CHMP’s review

Upon its initial review, the CHMP was concerned that data from the main study of plitidepsin in MM—the phase 3 ADMYRE trial—did not demonstrate a sufficient benefit of plitidepsin plus dexamethasone, compared to dexamethasone alone, in MM patients who had received 3 to 6 prior therapies.

The CHMP noted that the data showed a modest increase in progression free-survival (PFS)—around 1 month—with plitidepsin. According to study investigators, the median PFS was 3.8 months in patients who received plitidepsin and 1.9 months in those who received dexamethasone alone. According to an independent review committee, the median PFS was 2.6 months and 1.7 months, respectively.

The CHMP also said improvement in overall survival (OS) was not sufficiently demonstrated in this trial. The median OS was 11.6 months in the plitidepsin arm and 6.4 months in the dexamethasone arm.

Finally, the CHMP noted that severe adverse events were reported more frequently in patients who received plitidepsin. The most common grade 3/4 treatment-related adverse events (in the plitidepsin and dexamethasone arms, respectively) were fatigue (10.8% vs 1.2%), myalgia (5.4% vs 0%), and nausea (3.6% vs 1.2%).

Rates of treatment discontinuation were 9% in the plitidepsin arm, 6.5% in the dexamethasone arm, and 13.5% among patients who crossed over from the dexamethasone arm to the plitidepsin arm. Patients were allowed to cross over if they progressed after at least 8 weeks of treatment.

Based on these data, the CHMP was of the opinion that the benefits of plitidepsin did not outweigh its risks, so the committee recommended refusal of marketing authorization. After re-examination, the CHMP remained of the same opinion.

The European Commission (EC) has the final say on the marketing authorization application for plitidepsin. Though it is not required to do so, the EC typically follows the CHMP’s advice. The EC makes its decision within 67 days of the CHMP’s opinion.

PharmaMar has not announced whether it plans to continue developing plitidepsin for MM patients if the EC refuses to authorize the drug, and the company did not respond to a request for comment.

About plitidepsin

Plitidepsin is an investigational anticancer agent of marine origin, originally obtained from the ascidian Aplidium albicans. The drug specifically binds to eEF1A2 and targets the non-canonical role of this protein, resulting in cancer cell death via apoptosis.

Plitidepsin is currently in clinical development for hematologic malignancies.

In a phase 1b trial (NCT02100657), researchers are evaluating plitidepsin in combination with bortezomib and dexamethasone for patients with relapsed/refractory MM.

In a phase 2 trial (NCT03117361), researchers are investigating plitidepsin in combination with bortezomib and dexamethasone for patients with MM that is refractory to both lenalidomide and bortezomib.

Plitidepsin has received orphan drug designation in the European Union and the US.

Health South Florida

LISBON—Post-transplant therapy including galinpepimut-S (GPS) may prolong progression-free survival (PFS) in patients with high-risk multiple myeloma (MM), according to new research.

In a phase 2 trial, MM patients who received GPS and lenalidomide or bortezomib after autologous stem cell transplant (ASCT) had a median PFS of 23.6 months.

“Currently, post-transplant maintenance therapies for these difficult-to-treat patients are seemingly limited, with PFS rarely exceeding 12 to 14 months,” said Guenther Koehne, MD, PhD, from Miami Cancer Institute of Baptist Health South Florida.

Dr Koehne presented results observed with lenalidomide/bortezomib maintenance plus GPS consolidation at the 44th Annual Meeting of the EBMT (abstract OS4-6).

The trial was supported by the Leo A. Guthart and Kathryn Medina Research Fund and SELLAS Life Sciences Group, the company developing GPS.

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after ASCT.

The goal of GPS therapy was to stimulate an immune response to prevent or delay MM progression. GPS is a cancer immunotherapeutic consisting of 4 modified peptide chains that induce an innate immune response against the WT1 antigen.

Patients began receiving GPS within 22 days of ASCT. They received 6 doses, administered subcutaneously with the oil emulsifier montanide every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent clinical, immune response, and correlative assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS as well as lenalidomide (n=18) or bortezomib (n=1) maintenance, starting on day 100 post-ASCT. They underwent clinical, immune response, and correlative assessment again, 2 to 4 weeks after the 12th GPS dose.

Results

Dr Koehne said GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. And 75% of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

Dr Koehne also said immune responses were linked to clinical activity. In patients who received all 12 doses of GPS (n=12), there was a “strong and bidirectional association” between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses and 81.8% (n=9) had CD8 immune responses.

Among patients who maintained immune response positivity, the CR/VGPR rate was 54.6% if CD4 immune response positivity to any of the 4 native GPS peptides was maintained and 44.0% if CD8 immune response positivity to any of the 4 native GPS peptides was maintained.

The PFS was 81% at 12 months and 62% at 18 months. The median PFS was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

Health South Florida

LISBON—Post-transplant therapy including galinpepimut-S (GPS) may prolong progression-free survival (PFS) in patients with high-risk multiple myeloma (MM), according to new research.

In a phase 2 trial, MM patients who received GPS and lenalidomide or bortezomib after autologous stem cell transplant (ASCT) had a median PFS of 23.6 months.

“Currently, post-transplant maintenance therapies for these difficult-to-treat patients are seemingly limited, with PFS rarely exceeding 12 to 14 months,” said Guenther Koehne, MD, PhD, from Miami Cancer Institute of Baptist Health South Florida.

Dr Koehne presented results observed with lenalidomide/bortezomib maintenance plus GPS consolidation at the 44th Annual Meeting of the EBMT (abstract OS4-6).

The trial was supported by the Leo A. Guthart and Kathryn Medina Research Fund and SELLAS Life Sciences Group, the company developing GPS.

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after ASCT.

The goal of GPS therapy was to stimulate an immune response to prevent or delay MM progression. GPS is a cancer immunotherapeutic consisting of 4 modified peptide chains that induce an innate immune response against the WT1 antigen.

Patients began receiving GPS within 22 days of ASCT. They received 6 doses, administered subcutaneously with the oil emulsifier montanide every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent clinical, immune response, and correlative assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS as well as lenalidomide (n=18) or bortezomib (n=1) maintenance, starting on day 100 post-ASCT. They underwent clinical, immune response, and correlative assessment again, 2 to 4 weeks after the 12th GPS dose.

Results

Dr Koehne said GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. And 75% of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

Dr Koehne also said immune responses were linked to clinical activity. In patients who received all 12 doses of GPS (n=12), there was a “strong and bidirectional association” between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses and 81.8% (n=9) had CD8 immune responses.

Among patients who maintained immune response positivity, the CR/VGPR rate was 54.6% if CD4 immune response positivity to any of the 4 native GPS peptides was maintained and 44.0% if CD8 immune response positivity to any of the 4 native GPS peptides was maintained.

The PFS was 81% at 12 months and 62% at 18 months. The median PFS was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

Health South Florida

LISBON—Post-transplant therapy including galinpepimut-S (GPS) may prolong progression-free survival (PFS) in patients with high-risk multiple myeloma (MM), according to new research.

In a phase 2 trial, MM patients who received GPS and lenalidomide or bortezomib after autologous stem cell transplant (ASCT) had a median PFS of 23.6 months.

“Currently, post-transplant maintenance therapies for these difficult-to-treat patients are seemingly limited, with PFS rarely exceeding 12 to 14 months,” said Guenther Koehne, MD, PhD, from Miami Cancer Institute of Baptist Health South Florida.

Dr Koehne presented results observed with lenalidomide/bortezomib maintenance plus GPS consolidation at the 44th Annual Meeting of the EBMT (abstract OS4-6).

The trial was supported by the Leo A. Guthart and Kathryn Medina Research Fund and SELLAS Life Sciences Group, the company developing GPS.

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after ASCT.

The goal of GPS therapy was to stimulate an immune response to prevent or delay MM progression. GPS is a cancer immunotherapeutic consisting of 4 modified peptide chains that induce an innate immune response against the WT1 antigen.

Patients began receiving GPS within 22 days of ASCT. They received 6 doses, administered subcutaneously with the oil emulsifier montanide every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent clinical, immune response, and correlative assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS as well as lenalidomide (n=18) or bortezomib (n=1) maintenance, starting on day 100 post-ASCT. They underwent clinical, immune response, and correlative assessment again, 2 to 4 weeks after the 12th GPS dose.

Results

Dr Koehne said GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. And 75% of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

Dr Koehne also said immune responses were linked to clinical activity. In patients who received all 12 doses of GPS (n=12), there was a “strong and bidirectional association” between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses and 81.8% (n=9) had CD8 immune responses.

Among patients who maintained immune response positivity, the CR/VGPR rate was 54.6% if CD4 immune response positivity to any of the 4 native GPS peptides was maintained and 44.0% if CD8 immune response positivity to any of the 4 native GPS peptides was maintained.

The PFS was 81% at 12 months and 62% at 18 months. The median PFS was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.

“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”

Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.

Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.

[email protected]

SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
 

A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.

“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”

Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.

Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.

[email protected]

SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
 

A high body mass index in both early and later adulthood increases the risk for developing multiple myeloma (MM), according to a prospective analysis.

“This association did not significantly differ by gender but was nonetheless slightly stronger in men,” wrote Catherine R. Marinac, PhD, of the Dana-Farber Cancer Institute, Boston, and her colleagues. “MM risk was significantly positively associated with weight change and suggestive of a positive association for change in BMI since young adulthood. In contrast, we did not observe statistically significant associations of cumulative average physical activity or walking with MM risk.”

Dr. Marinac and her associates analyzed participants from the Nurses’ Health Study (NHS), the Health Professionals Follow-Up Study (HPFS), and the Women’s Health Study (WHS) with a pooled total of 575 MM cases and more than 5 million person-years of follow-up. From all of those databases, a combined baseline total of 49,374 men and 153,260 women were included in the analyses. Participants in all three of the cohorts were predominately white.

Each participant was required to report height and weight on a baseline questionnaire and updated weights on subsequent questionnaires. Using that height and weight information, the researchers calculated BMI. Physical activity also was reported using questionnaires, beginning in 1986 in the HPFS and NHS groups and at baseline for WHS, with all groups providing updates every 2-4 years. The researchers used the physical activity information to calculate the total metabolic equivalent (MET) hours of all activity and of walking per week.

[email protected]

SOURCE: Marinac CR et al. Br J Cancer. 2018 Mar 12. doi: 10.1038/s41416-018-0010-4.
 

A third autologous stem cell transplantation (ASCT) is feasible and provides clinical benefit to patients with relapsed multiple myeloma, according to findings from a retrospective study.

The benefits appear to be most pronounced in patients who had a long duration of response to the previous ASCT, the researchers wrote in Biology of Blood and Marrow Transplantation.

“A salvage third ASCT is of value for patients with relapsed multiple myeloma,” Laurent Garderet, MD, of the department of hematology, Hôpital Saint Antoine, Paris, and coauthors wrote in the report.

A third transplantation is most commonly used in patients who relapse following tandem ASCT. Less often, it is done in patients who receive upfront ASCT, relapse, undergo a second ASCT, and relapse again.

“The first scenario gives much better results, due in part to a better remission status at the third ASCT with no signs of increased [second primary malignancy],” the researchers wrote.

In that group, median overall survival was greater than 5 years if the relapse occurred 3 years or more after the initial tandem ASCT, study results show.

The retrospective analysis, based on European Society for Blood and Marrow Transplantation data, included 570 patients who had undergone a third ASCT between 1997 and 2010. Of that group, 482 patients (81%) received the third transplantation after tandem ASCT and subsequent relapse, and 88 (15%) received it after second relapse.

After third ASCT, overall survival was 33 months in the larger tandem transplant group with 61 months of follow-up, and 15 months in the smaller group of patients who received two salvage ASCTs after 48 months of follow-up.

Median progression-free survival was 13 and 8 months for the tandem ASCT and two-salvage–ASCT groups, respectively, while 100-day nonrelapse mortality was 4% and 7%, respectively.

For both groups, better outcomes were associated with longer duration of remission after the second ASCT, the researchers reported.

Moreover, the time from second ASCT to relapse was the only favorable prognostic factor associated with survival after third ASCT in a multivariate analysis of the patients who relapsed following tandem transplant. The hazard ratio for relapse occurring between 18 and 36 months vs. within 18 months was 0.62 (95% confidence interval, 0.47-0.82; P = .01); for relapse after 36 months, the HR was 0.35 (95% CI, 0.25-0.49; P less than .001).

The researchers acknowledged that, beyond transplant, treatment of myeloma has changed substantially in recent years and could change the clinical picture for patients undergoing a third ASCT.

“The availability of novel agents may further improve the response to a third ASCT, rather than impairing its usefulness in the salvage setting, by enhancing the depth of response before ASCT, which could result in improved durability of the outcome,” they wrote.

The researchers reported having no financial disclosures related to this study.

SOURCE: Garderet L et al. Biol Blood Marrow Transplant. 2018 Feb 3. doi: 10.1016/j.bbmt.2018.01.035.

A third autologous stem cell transplantation (ASCT) is feasible and provides clinical benefit to patients with relapsed multiple myeloma, according to findings from a retrospective study.

The benefits appear to be most pronounced in patients who had a long duration of response to the previous ASCT, the researchers wrote in Biology of Blood and Marrow Transplantation.

“A salvage third ASCT is of value for patients with relapsed multiple myeloma,” Laurent Garderet, MD, of the department of hematology, Hôpital Saint Antoine, Paris, and coauthors wrote in the report.

A third transplantation is most commonly used in patients who relapse following tandem ASCT. Less often, it is done in patients who receive upfront ASCT, relapse, undergo a second ASCT, and relapse again.

“The first scenario gives much better results, due in part to a better remission status at the third ASCT with no signs of increased [second primary malignancy],” the researchers wrote.

In that group, median overall survival was greater than 5 years if the relapse occurred 3 years or more after the initial tandem ASCT, study results show.

The retrospective analysis, based on European Society for Blood and Marrow Transplantation data, included 570 patients who had undergone a third ASCT between 1997 and 2010. Of that group, 482 patients (81%) received the third transplantation after tandem ASCT and subsequent relapse, and 88 (15%) received it after second relapse.

After third ASCT, overall survival was 33 months in the larger tandem transplant group with 61 months of follow-up, and 15 months in the smaller group of patients who received two salvage ASCTs after 48 months of follow-up.

Median progression-free survival was 13 and 8 months for the tandem ASCT and two-salvage–ASCT groups, respectively, while 100-day nonrelapse mortality was 4% and 7%, respectively.

For both groups, better outcomes were associated with longer duration of remission after the second ASCT, the researchers reported.

Moreover, the time from second ASCT to relapse was the only favorable prognostic factor associated with survival after third ASCT in a multivariate analysis of the patients who relapsed following tandem transplant. The hazard ratio for relapse occurring between 18 and 36 months vs. within 18 months was 0.62 (95% confidence interval, 0.47-0.82; P = .01); for relapse after 36 months, the HR was 0.35 (95% CI, 0.25-0.49; P less than .001).

The researchers acknowledged that, beyond transplant, treatment of myeloma has changed substantially in recent years and could change the clinical picture for patients undergoing a third ASCT.

“The availability of novel agents may further improve the response to a third ASCT, rather than impairing its usefulness in the salvage setting, by enhancing the depth of response before ASCT, which could result in improved durability of the outcome,” they wrote.

The researchers reported having no financial disclosures related to this study.

SOURCE: Garderet L et al. Biol Blood Marrow Transplant. 2018 Feb 3. doi: 10.1016/j.bbmt.2018.01.035.

A third autologous stem cell transplantation (ASCT) is feasible and provides clinical benefit to patients with relapsed multiple myeloma, according to findings from a retrospective study.

The benefits appear to be most pronounced in patients who had a long duration of response to the previous ASCT, the researchers wrote in Biology of Blood and Marrow Transplantation.

“A salvage third ASCT is of value for patients with relapsed multiple myeloma,” Laurent Garderet, MD, of the department of hematology, Hôpital Saint Antoine, Paris, and coauthors wrote in the report.

A third transplantation is most commonly used in patients who relapse following tandem ASCT. Less often, it is done in patients who receive upfront ASCT, relapse, undergo a second ASCT, and relapse again.

“The first scenario gives much better results, due in part to a better remission status at the third ASCT with no signs of increased [second primary malignancy],” the researchers wrote.

In that group, median overall survival was greater than 5 years if the relapse occurred 3 years or more after the initial tandem ASCT, study results show.

The retrospective analysis, based on European Society for Blood and Marrow Transplantation data, included 570 patients who had undergone a third ASCT between 1997 and 2010. Of that group, 482 patients (81%) received the third transplantation after tandem ASCT and subsequent relapse, and 88 (15%) received it after second relapse.

After third ASCT, overall survival was 33 months in the larger tandem transplant group with 61 months of follow-up, and 15 months in the smaller group of patients who received two salvage ASCTs after 48 months of follow-up.

Median progression-free survival was 13 and 8 months for the tandem ASCT and two-salvage–ASCT groups, respectively, while 100-day nonrelapse mortality was 4% and 7%, respectively.

For both groups, better outcomes were associated with longer duration of remission after the second ASCT, the researchers reported.

Moreover, the time from second ASCT to relapse was the only favorable prognostic factor associated with survival after third ASCT in a multivariate analysis of the patients who relapsed following tandem transplant. The hazard ratio for relapse occurring between 18 and 36 months vs. within 18 months was 0.62 (95% confidence interval, 0.47-0.82; P = .01); for relapse after 36 months, the HR was 0.35 (95% CI, 0.25-0.49; P less than .001).

The researchers acknowledged that, beyond transplant, treatment of myeloma has changed substantially in recent years and could change the clinical picture for patients undergoing a third ASCT.

“The availability of novel agents may further improve the response to a third ASCT, rather than impairing its usefulness in the salvage setting, by enhancing the depth of response before ASCT, which could result in improved durability of the outcome,” they wrote.

The researchers reported having no financial disclosures related to this study.

SOURCE: Garderet L et al. Biol Blood Marrow Transplant. 2018 Feb 3. doi: 10.1016/j.bbmt.2018.01.035.

Photo by Rhoda Baer

New research suggests guidelines from the National Comprehensive Cancer Network (NCCN) may sometimes be supported by low-quality evidence or no evidence at all.

Researchers compared NCCN recommendations for cancer drugs to US cancer drug approvals over a 5-year period.

Thirty-nine percent of NCCN’s treatment recommendations did not coincide with uses approved by the US Food and Drug Administration (FDA).

For most of these recommendations (84%), NCCN did not provide supporting data from randomized, phase 3 trials.

For 36% of the recommendations, NCCN gave no supporting evidence.

Vinay Prasad, MD, of Oregon Health & Science University in Portland, Oregon, and his colleagues reported these findings in The BMJ.

Dr Prasad and his colleagues compared FDA approvals of cancer drugs between 2011 and 2015 with NCCN recommendations as of March 25, 2016.

When NCCN made recommendations beyond FDA approvals, the researchers evaluated the evidence used to support those recommendations.

Forty-seven new cancer drugs were approved by the FDA for 69 indications between 2011 and 2015. NCCN recommended the 47 drugs for 113 indications, including the 69 FDA-approved indications.

So 39% (n=44) of NCCN’s recommendations were not approved by the FDA, and NCCN gave the following evidence to support these recommendations:

• No evidence—36% (n=16)
• Phase 2 trial without randomization—30% (n=13)
• Randomized, phase 3 trial—16% (n=7)
• Phase 2 trial with randomization—7% (n=3)
• Case report or series of less than 5 patients—5% (n=2)
• Book chapter or review article—2% (n=1)
• Phase 1 trial—2% (n=1)
• Ongoing trial—2% (n=1).

Dr Prasad and his colleagues did point out that not all FDA approvals are supported by randomized, phase 3 trials.

And when the team followed-up 21 months after their initial analysis, they found that 6 of the 44 (14%) additional recommendations by NCCN had received FDA approval.

The researchers also noted that they did not search for independent evidence to support NCCN recommendations beyond the references NCCN provided. So some of the recommendations may have had more or better supporting evidence than what was provided.

Still, the team said these results suggest NCCN “frequently” makes recommendations that go beyond FDA approvals and “often fails to cite evidence or relies on low levels of evidence.” Therefore, NCCN should cite all evidence used to formulate its recommendations.

NCCN argues that it does provide ample evidence to support the recommendations in its guidelines.

“The NCCN guidelines contain more than 24,500 references to inform users of the evidence used in making its decisions,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“These data are supplemented by the analysis of the available evidence by expert clinician researchers and patient advocates who evaluate each recommendation and come to consensus. Each recommendation is labeled with a Category of Evidence, and the vast majority of those for systemic therapies are accompanied by Evidence Blocks, which outline, on 1-5 scales, the efficacy, safety, quality of the evidence, consistency of the evidence, and affordability of the treatment.”

Photo by Rhoda Baer

New research suggests guidelines from the National Comprehensive Cancer Network (NCCN) may sometimes be supported by low-quality evidence or no evidence at all.

Researchers compared NCCN recommendations for cancer drugs to US cancer drug approvals over a 5-year period.

Thirty-nine percent of NCCN’s treatment recommendations did not coincide with uses approved by the US Food and Drug Administration (FDA).

For most of these recommendations (84%), NCCN did not provide supporting data from randomized, phase 3 trials.

For 36% of the recommendations, NCCN gave no supporting evidence.

Vinay Prasad, MD, of Oregon Health & Science University in Portland, Oregon, and his colleagues reported these findings in The BMJ.

Dr Prasad and his colleagues compared FDA approvals of cancer drugs between 2011 and 2015 with NCCN recommendations as of March 25, 2016.

When NCCN made recommendations beyond FDA approvals, the researchers evaluated the evidence used to support those recommendations.

Forty-seven new cancer drugs were approved by the FDA for 69 indications between 2011 and 2015. NCCN recommended the 47 drugs for 113 indications, including the 69 FDA-approved indications.

So 39% (n=44) of NCCN’s recommendations were not approved by the FDA, and NCCN gave the following evidence to support these recommendations:

• No evidence—36% (n=16)
• Phase 2 trial without randomization—30% (n=13)
• Randomized, phase 3 trial—16% (n=7)
• Phase 2 trial with randomization—7% (n=3)
• Case report or series of less than 5 patients—5% (n=2)
• Book chapter or review article—2% (n=1)
• Phase 1 trial—2% (n=1)
• Ongoing trial—2% (n=1).

Dr Prasad and his colleagues did point out that not all FDA approvals are supported by randomized, phase 3 trials.

And when the team followed-up 21 months after their initial analysis, they found that 6 of the 44 (14%) additional recommendations by NCCN had received FDA approval.

The researchers also noted that they did not search for independent evidence to support NCCN recommendations beyond the references NCCN provided. So some of the recommendations may have had more or better supporting evidence than what was provided.

Still, the team said these results suggest NCCN “frequently” makes recommendations that go beyond FDA approvals and “often fails to cite evidence or relies on low levels of evidence.” Therefore, NCCN should cite all evidence used to formulate its recommendations.

NCCN argues that it does provide ample evidence to support the recommendations in its guidelines.

“The NCCN guidelines contain more than 24,500 references to inform users of the evidence used in making its decisions,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“These data are supplemented by the analysis of the available evidence by expert clinician researchers and patient advocates who evaluate each recommendation and come to consensus. Each recommendation is labeled with a Category of Evidence, and the vast majority of those for systemic therapies are accompanied by Evidence Blocks, which outline, on 1-5 scales, the efficacy, safety, quality of the evidence, consistency of the evidence, and affordability of the treatment.”

Photo by Rhoda Baer

New research suggests guidelines from the National Comprehensive Cancer Network (NCCN) may sometimes be supported by low-quality evidence or no evidence at all.

Researchers compared NCCN recommendations for cancer drugs to US cancer drug approvals over a 5-year period.

Thirty-nine percent of NCCN’s treatment recommendations did not coincide with uses approved by the US Food and Drug Administration (FDA).

For most of these recommendations (84%), NCCN did not provide supporting data from randomized, phase 3 trials.

For 36% of the recommendations, NCCN gave no supporting evidence.

Vinay Prasad, MD, of Oregon Health & Science University in Portland, Oregon, and his colleagues reported these findings in The BMJ.

Dr Prasad and his colleagues compared FDA approvals of cancer drugs between 2011 and 2015 with NCCN recommendations as of March 25, 2016.

When NCCN made recommendations beyond FDA approvals, the researchers evaluated the evidence used to support those recommendations.

Forty-seven new cancer drugs were approved by the FDA for 69 indications between 2011 and 2015. NCCN recommended the 47 drugs for 113 indications, including the 69 FDA-approved indications.

So 39% (n=44) of NCCN’s recommendations were not approved by the FDA, and NCCN gave the following evidence to support these recommendations:

• No evidence—36% (n=16)
• Phase 2 trial without randomization—30% (n=13)
• Randomized, phase 3 trial—16% (n=7)
• Phase 2 trial with randomization—7% (n=3)
• Case report or series of less than 5 patients—5% (n=2)
• Book chapter or review article—2% (n=1)
• Phase 1 trial—2% (n=1)
• Ongoing trial—2% (n=1).

Dr Prasad and his colleagues did point out that not all FDA approvals are supported by randomized, phase 3 trials.

And when the team followed-up 21 months after their initial analysis, they found that 6 of the 44 (14%) additional recommendations by NCCN had received FDA approval.

The researchers also noted that they did not search for independent evidence to support NCCN recommendations beyond the references NCCN provided. So some of the recommendations may have had more or better supporting evidence than what was provided.

Still, the team said these results suggest NCCN “frequently” makes recommendations that go beyond FDA approvals and “often fails to cite evidence or relies on low levels of evidence.” Therefore, NCCN should cite all evidence used to formulate its recommendations.

NCCN argues that it does provide ample evidence to support the recommendations in its guidelines.

“The NCCN guidelines contain more than 24,500 references to inform users of the evidence used in making its decisions,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“These data are supplemented by the analysis of the available evidence by expert clinician researchers and patient advocates who evaluate each recommendation and come to consensus. Each recommendation is labeled with a Category of Evidence, and the vast majority of those for systemic therapies are accompanied by Evidence Blocks, which outline, on 1-5 scales, the efficacy, safety, quality of the evidence, consistency of the evidence, and affordability of the treatment.”