Caleb Rans

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

The combination of ado-trastuzumab emtansine (T-DM1) and neratinib shows promise in patients with HER2-positive metastatic breast cancer, according to results from a phase 1b trial.

“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.

The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.

“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.

“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.

With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.

After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.

Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.

Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.

Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.

The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.

SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.

The combination of ado-trastuzumab emtansine (T-DM1) and neratinib shows promise in patients with HER2-positive metastatic breast cancer, according to results from a phase 1b trial.

“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.

The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.

“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.

“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.

With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.

After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.

Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.

Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.

Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.

The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.

SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.

The combination of ado-trastuzumab emtansine (T-DM1) and neratinib shows promise in patients with HER2-positive metastatic breast cancer, according to results from a phase 1b trial.

“The purpose of this study was to determine the safety and preliminary efficacy of the combination in patients previously treated with trastuzumab plus pertuzumab,” wrote Jame Abraham, MD, of the Cleveland Clinic and colleagues in the Journal of Clinical Oncology.

The open-label, dose-escalation study included 27 women with HER2-positive metastatic breast cancer who had hormone receptor–positive or hormone receptor–negative disease. All participants had demonstrated disease progression, despite prior treatment with combination pertuzumab and trastuzumab, plus a taxane. Among 19 response-evaluable patients, 12 patients (63%) had an objective response. Responses were observed across all neratinib doses, including a complete response in three patients, and partial response in nine patients.

“Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification,” Dr. Abraham and associates noted.

“Alterations in the expression of specific HER2 species in ERBB2-amplified cancers, including p95HER2, may have therapeutic implications and require further investigation,” they wrote.

With respect to neratinib dosing, the initial cohort was started at 120 mg daily, which was increased to 240 mg daily in successive cohorts using a 3+3 design. T-DM1 was administered every 3 weeks at 3.6 mg/kg.

After analysis, the researchers proposed a phase 2 dose of neratinib 160 mg once daily and T-DM1 3.6 mg/kg for the combination.

Dose-limiting grade 3 diarrhea was reported in a total of six patients, which was most pronounced in cycle 1. At the phase 2 recommended dose of neratinib, 7 of 10 patients had early-onset diarrhea, which resolved within 24 hours. No grade 4-5 diarrheal toxicities were reported.

Other grade 3-4 adverse events observed were electrolyte abnormalities, thrombocytopenia, nausea, and dehydration.

Phase 2 studies are currently ongoing in order to better characterize the activity of combination T-DM1 and neratinib.

The study was funded by PUMA Biotechnology and the University of Pittsburgh. The authors reported financial affiliations with AstraZeneca, Eisai, Genentech, Guardant Health, Pfizer, Roche, Seattle Genetics, and several others.

SOURCE: Abraham J et al. J Clin Oncol. 2019 Aug 23. doi: 10.1200/JCO.19.00858.

Novel extended half-life factor VIII (FVIII) and factor IX (FIX) products appear to decrease the number of infusions and maintain higher trough levels, especially for patients with hemophilia B, according to recent survey findings.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Preliminary data from a European multinational survey suggest these benefits may help overcome current limitations with standard clotting factor products.

“We administered a survey to determine the efficacy of [extended half-life] products after they became available in several European countries,” wrote Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues. These results were published in Haemophilia.

The questionnaire, designed by the European Association for Haemophilia and Allied Disorders (EAHAD), was distributed to 48 hemophilia treatment centers in January 2018. In total, 33 centers completed the survey.

The survey explored the real-life clinical experiences of patients with hemophilia A and B using extended half-life FVIII and FIX products. At the time of the survey, pegylated factor products were not available for use. In particular, the survey collected general information related to the efficacy of prophylaxis after transitioning patients to novel extended half-life products.

After analysis, the researchers found that among responding centers, extended half-life FVIII products decreased the number of infusions by 30% or greater among hemophilia A patients and achieved trough levels of 3%-5% in 66%-67% of centers.

With respect to FIX products, all responding centers were able to reduce infusions by more than 30% among hemophilia B patients, with 67% maintaining a FIX trough level of no less than 5%-10%.

The researchers acknowledged that the findings are preliminary and should be confirmed by conducting a repeat survey.

“Evaluating the safety of these new drugs is of the utmost importance and should be monitored through careful, long‐term observation,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Alnylam, Grifols, Kedrion, Pfizer, Roche, Sanofi, Bayer, Shire, and several other companies.

SOURCE: Peyvandi F et al. Haemophilia. 2019 Aug 16. doi: 10.1111/hae.13834.

Novel extended half-life factor VIII (FVIII) and factor IX (FIX) products appear to decrease the number of infusions and maintain higher trough levels, especially for patients with hemophilia B, according to recent survey findings.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Preliminary data from a European multinational survey suggest these benefits may help overcome current limitations with standard clotting factor products.

“We administered a survey to determine the efficacy of [extended half-life] products after they became available in several European countries,” wrote Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues. These results were published in Haemophilia.

The questionnaire, designed by the European Association for Haemophilia and Allied Disorders (EAHAD), was distributed to 48 hemophilia treatment centers in January 2018. In total, 33 centers completed the survey.

The survey explored the real-life clinical experiences of patients with hemophilia A and B using extended half-life FVIII and FIX products. At the time of the survey, pegylated factor products were not available for use. In particular, the survey collected general information related to the efficacy of prophylaxis after transitioning patients to novel extended half-life products.

After analysis, the researchers found that among responding centers, extended half-life FVIII products decreased the number of infusions by 30% or greater among hemophilia A patients and achieved trough levels of 3%-5% in 66%-67% of centers.

With respect to FIX products, all responding centers were able to reduce infusions by more than 30% among hemophilia B patients, with 67% maintaining a FIX trough level of no less than 5%-10%.

The researchers acknowledged that the findings are preliminary and should be confirmed by conducting a repeat survey.

“Evaluating the safety of these new drugs is of the utmost importance and should be monitored through careful, long‐term observation,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Alnylam, Grifols, Kedrion, Pfizer, Roche, Sanofi, Bayer, Shire, and several other companies.

SOURCE: Peyvandi F et al. Haemophilia. 2019 Aug 16. doi: 10.1111/hae.13834.

Novel extended half-life factor VIII (FVIII) and factor IX (FIX) products appear to decrease the number of infusions and maintain higher trough levels, especially for patients with hemophilia B, according to recent survey findings.

Crystal/Wikimedia Commons/Creative Commons Attribution 2.0

Preliminary data from a European multinational survey suggest these benefits may help overcome current limitations with standard clotting factor products.

“We administered a survey to determine the efficacy of [extended half-life] products after they became available in several European countries,” wrote Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues. These results were published in Haemophilia.

The questionnaire, designed by the European Association for Haemophilia and Allied Disorders (EAHAD), was distributed to 48 hemophilia treatment centers in January 2018. In total, 33 centers completed the survey.

The survey explored the real-life clinical experiences of patients with hemophilia A and B using extended half-life FVIII and FIX products. At the time of the survey, pegylated factor products were not available for use. In particular, the survey collected general information related to the efficacy of prophylaxis after transitioning patients to novel extended half-life products.

After analysis, the researchers found that among responding centers, extended half-life FVIII products decreased the number of infusions by 30% or greater among hemophilia A patients and achieved trough levels of 3%-5% in 66%-67% of centers.

With respect to FIX products, all responding centers were able to reduce infusions by more than 30% among hemophilia B patients, with 67% maintaining a FIX trough level of no less than 5%-10%.

The researchers acknowledged that the findings are preliminary and should be confirmed by conducting a repeat survey.

“Evaluating the safety of these new drugs is of the utmost importance and should be monitored through careful, long‐term observation,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Alnylam, Grifols, Kedrion, Pfizer, Roche, Sanofi, Bayer, Shire, and several other companies.

SOURCE: Peyvandi F et al. Haemophilia. 2019 Aug 16. doi: 10.1111/hae.13834.

Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.

Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.

“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.

The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.

Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.

In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).

With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.

“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.

One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.

“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.

Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.

Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.

“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.

The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.

Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.

In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).

With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.

“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.

One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.

“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.

Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.

Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.

“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.

The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.

Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.

In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).

With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.

“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.

One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.

“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.

The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.

SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.

A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.

“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.

The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.

The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.

Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.

After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.

Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.

The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.

They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.

The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.

The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.

SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.

A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.

“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.

The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.

The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.

Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.

After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.

Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.

The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.

They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.

The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.

The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.

SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.

A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.

“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.

The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.

The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.

Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.

After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.

Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.

The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.

They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.

The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.

The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.

SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.

Perceived everyday discrimination was associated with an extended duration between symptom onset and cancer diagnosis (prolonged symptom duration) in black women with ovarian cancer, according to results from a case-control analysis.

In contrast, another interpersonal factor, trust in physicians, was not associated with prolonged symptom duration.

“We [examined] the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis,” wrote Megan A. Mullins, MPH, of the University of Michigan, Ann Arbor, and colleagues. The findings were published in Cancer.

The analysis included 486 cases of black women with newly diagnosed epithelial ovarian cancer, 302 of whom had prolonged symptom duration. Study cases were obtained from the African American Cancer Epidemiology Study that took place from December 2010 to December 2015. Perceived discrimination was evaluated with the five-question version of the Williams Everyday Discrimination Scale.

In the model, adjustments were made for various demographic characteristics, including marital status, body mass index, and age at diagnosis, among other parameters.

After analysis, the researchers found that every 1-unit rise in the frequency of everyday discrimination was associated with a higher likelihood of prolonged symptom duration (odds ratio, 1.74; 95% confidence interval, 1.22-2.49).

No association was found between trust in physicians and prolonged symptom duration (odds ratio, 0.86; 95% CI, 0.66-1.11).

“These results point to the social context in daily life playing a role in receiving optimal ovarian cancer care,” the researchers wrote.

One key limitation of the study was that the data was obtained in a cross-sectional manner, which could introduce bias because of reverse causality.

“This work is a novel first step in understanding the relationship between interpersonal exposures and racial disparities in ovarian cancer care. More equitable access to ovarian cancer care necessitates that women feel comfortable about advocating for their needs and trust their self-assessment of their symptoms,” they concluded.

The study was funded by the National Cancer Institute, the Metropolitan Detroit Cancer Surveillance System, and the Epidemiology Research Core. The authors reported no conflicts of interest.
 

SOURCE: Mullins MA et al. Cancer. 2019 Aug 15. doi: 10.1002/cncr.32451.

Perceived everyday discrimination was associated with an extended duration between symptom onset and cancer diagnosis (prolonged symptom duration) in black women with ovarian cancer, according to results from a case-control analysis.

In contrast, another interpersonal factor, trust in physicians, was not associated with prolonged symptom duration.

“We [examined] the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis,” wrote Megan A. Mullins, MPH, of the University of Michigan, Ann Arbor, and colleagues. The findings were published in Cancer.

The analysis included 486 cases of black women with newly diagnosed epithelial ovarian cancer, 302 of whom had prolonged symptom duration. Study cases were obtained from the African American Cancer Epidemiology Study that took place from December 2010 to December 2015. Perceived discrimination was evaluated with the five-question version of the Williams Everyday Discrimination Scale.

In the model, adjustments were made for various demographic characteristics, including marital status, body mass index, and age at diagnosis, among other parameters.

After analysis, the researchers found that every 1-unit rise in the frequency of everyday discrimination was associated with a higher likelihood of prolonged symptom duration (odds ratio, 1.74; 95% confidence interval, 1.22-2.49).

No association was found between trust in physicians and prolonged symptom duration (odds ratio, 0.86; 95% CI, 0.66-1.11).

“These results point to the social context in daily life playing a role in receiving optimal ovarian cancer care,” the researchers wrote.

One key limitation of the study was that the data was obtained in a cross-sectional manner, which could introduce bias because of reverse causality.

“This work is a novel first step in understanding the relationship between interpersonal exposures and racial disparities in ovarian cancer care. More equitable access to ovarian cancer care necessitates that women feel comfortable about advocating for their needs and trust their self-assessment of their symptoms,” they concluded.

The study was funded by the National Cancer Institute, the Metropolitan Detroit Cancer Surveillance System, and the Epidemiology Research Core. The authors reported no conflicts of interest.
 

SOURCE: Mullins MA et al. Cancer. 2019 Aug 15. doi: 10.1002/cncr.32451.

Perceived everyday discrimination was associated with an extended duration between symptom onset and cancer diagnosis (prolonged symptom duration) in black women with ovarian cancer, according to results from a case-control analysis.

In contrast, another interpersonal factor, trust in physicians, was not associated with prolonged symptom duration.

“We [examined] the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis,” wrote Megan A. Mullins, MPH, of the University of Michigan, Ann Arbor, and colleagues. The findings were published in Cancer.

The analysis included 486 cases of black women with newly diagnosed epithelial ovarian cancer, 302 of whom had prolonged symptom duration. Study cases were obtained from the African American Cancer Epidemiology Study that took place from December 2010 to December 2015. Perceived discrimination was evaluated with the five-question version of the Williams Everyday Discrimination Scale.

In the model, adjustments were made for various demographic characteristics, including marital status, body mass index, and age at diagnosis, among other parameters.

After analysis, the researchers found that every 1-unit rise in the frequency of everyday discrimination was associated with a higher likelihood of prolonged symptom duration (odds ratio, 1.74; 95% confidence interval, 1.22-2.49).

No association was found between trust in physicians and prolonged symptom duration (odds ratio, 0.86; 95% CI, 0.66-1.11).

“These results point to the social context in daily life playing a role in receiving optimal ovarian cancer care,” the researchers wrote.

One key limitation of the study was that the data was obtained in a cross-sectional manner, which could introduce bias because of reverse causality.

“This work is a novel first step in understanding the relationship between interpersonal exposures and racial disparities in ovarian cancer care. More equitable access to ovarian cancer care necessitates that women feel comfortable about advocating for their needs and trust their self-assessment of their symptoms,” they concluded.

The study was funded by the National Cancer Institute, the Metropolitan Detroit Cancer Surveillance System, and the Epidemiology Research Core. The authors reported no conflicts of interest.
 

SOURCE: Mullins MA et al. Cancer. 2019 Aug 15. doi: 10.1002/cncr.32451.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

The use of nivolumab is associated with a long-term survival benefit, compared with docetaxel in patients with previously treated advanced non–small cell lung cancer (NSCLC), according to a pooled analysis of four trials.

The survival outcomes comparing the two therapies demonstrates an extended survival advantage for nivolumab up to and past a duration of 4 years.

“We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival,” wrote Scott J. Antonia, MD, PhD, formally of the H. Lee Moffitt Cancer Center in Tampa and now at Duke Cancer Center, Durham, N.C., and colleagues. The findings were published in the Lancet Oncology.

The researchers combined data from four clinical studies (CheckMate 003, 017, 057, and 063) that assessed survival outcomes in patients receiving second-line or later nivolumab therapy. Across the four trials, a total of 664 patients were administered nivolumab.

The CheckMate 057 and 017 phase 3, randomized clinical trials compared docetaxel versus nivolumab in patients with previously treated nonsquamous and squamous NSCLC, respectively.

With respect to safety analyses, Dr. Antonia and colleagues included patients who were administered a minimum of one dose of nivolumab.

Across the four trials, the 4-year overall survival with nivolumab was 14% (11%-17%), including 11% (7%-16%) for patients with under 1% programmed death–ligand 1 expression, and 19% (15%-24%) for patients with a minimum of 1% programmed death–ligand 1 expression.

In CheckMate 057 and 017, the 4-year overall survival with nivolumab was 14% (11%-18%) versus 5% (3%-7%) in patients who received docetaxel.

With respect to safety, analysis of the long-term data did not reveal any novel safety signals.

The researchers acknowledged that a key limitation of the study was the exclusion of patients who were maintained in stable disease or in response at the point of data lock.

As a result, the findings likely minimize the survival advantage seen post–disease progression for nivolumab, compared with docetaxel.

“Additional analyses assessing the effect of various factors on long-term survival with immunotherapy versus chemotherapy are planned,” they wrote.

The study was funded by Bristol-Myers Squibb. The authors reported financial affiliations with AstraZeneca, Boehringer Ingelheim, Cellular Biomedicine Group, FLX Bio, Genentech, Novartis, Regeneron, and several others.

SOURCE: Antonia SJ et al. Lancet Oncol. 2019 Aug 14. doi: 10.1016/S1470-2045(19)30407-3.

Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.

“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.

The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.

Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.

Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.

The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.

After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.

The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).

“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.

With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.

The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.

Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.

“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.

The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.

Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.

Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.

The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.

After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.

The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).

“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.

With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.

The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.

Obinutuzumab plus lenalidomide showed manageable safety and activity in patients with relapsed/refractory follicular lymphoma (FL), according to results from a phase 2 trial.

“The results of this phase 2 study show that induction therapy with obinutuzumab and lenalidomide followed by maintenance therapy with obinutuzumab is effective for many patients with relapsed or refractory follicular lymphoma,” wrote Franck Morschhauser, MD, PhD, of the University of Lille, France, and colleagues. The results were published in The Lancet Haematology.

The multicenter, single-arm study comprised 89 patients, 88 of whom were assessed for safety and 86 for efficacy. All eligible study patients received a minimum of one prior rituximab-based therapy before receiving obinutuzumab.

Study participants received intravenous obinutuzumab 1,000 mg for six 28-day cycles, in addition to oral lenalidomide 20 mg as induction therapy.

Maintenance therapy (year 1) consisted of oral lenalidomide 10 mg on days 2-22 of each cycle for a maximum of 12 28-day cycles plus obinutuzumab 1,000 mg on day 1 of alternate cycles (total of six infusions). Maintenance therapy (year 2) consisted of obinutuzumab 1,000 mg alone on day 1 for six 56-day cycles.

The primary outcome was the proportion of patients who achieved an overall response at the end of induction therapy. Secondary outcomes included various survival parameters and safety.

After analysis, the researchers found that the proportion of patients who achieved an overall response at induction end was 79% (95% confidence interval, 69-87). In addition, 38% of patients (95% CI, 28-50) had achieved a complete response at the end of induction therapy.

The progression-free survival, event-free survival, and overall survival rates were 65% (95% CI, 54-74), 62% (95% CI, 51-72), and 87% (95% CI, 78-93), respectively, at 2 years (no P values were reported).

“The results suggest that obinutuzumab plus lenalidomide is active as shown by 2-year outcomes (progression-free survival and overall survival) in the overall patient group,” the researchers wrote.

With respect to safety, basal cell carcinoma (6%), febrile neutropenia (5%), and infusion-related reactions (3%) were the most frequently reported serious toxicities. One patient died because of therapy-related febrile neutropenia.

The Lymphoma Academic Research Organisation, Celgene, and Roche funded the study. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Morschhauser F et al. Lancet Haematol. 2019 Jul 8. doi: 10.1016/S2352-3026(19)30089-4.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Men with severe hemophilia A showed reduced levels of bone mineral density, compared with controls representative of the general population, according to findings from a case-control study.

In addition, the decrease in bone mineral density (BMD) was correlated with reduced functional ability and body mass index (BMI), and vitamin D insufficiency or deficiency.

“We aimed to investigate the presence of low BMD in adult patients diagnosed with severe hemophilia A and to evaluate the potential risk factors associated with low BMD and musculoskeletal function levels,” wrote Omer Ekinci, MD, of Firat University in Elazig, Turkey, and colleagues in Haemophilia.

The study included 41 men with severe hemophilia A and 40 men without hemophilia who were matched for age. All patients with hemophilia A received regular prophylactic therapy, and one patient had a high titre (greater than 5 Bethesda units) inhibitor against FVIII.

The researchers performed several laboratory tests: BMD was measured using dual-energy x-ray absorptiometry; BMI was recorded; and laboratory tests were performed to ascertain levels of vitamin D, calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and hepatitis C and HIV antibodies. The Functional Independence Score in Hemophilia (FISH) was used to measure functional-ability status only in the study group.

After analysis, the researchers found a significant difference between patients in the case and control groups for femoral neck and total hip BMD (P = .017 and P less than .001, respectively), but not for lumbar spine BMD (P = .071).

In patients with hemophilia aged younger than 50 years, 27.8% were found to have “low normal” BMD levels, and 19.4% showed “lower than expected” BMD levels with respect to age.

“Vitamin D insufficiency and deficiency were present in 63.4% of the patients with hemophilia, significantly higher than the control group [37.5%; P less than .001],” the researchers wrote.

There were also statistically significant positive correlations between FISH score and femoral neck BMD (P = .001, r = .530), femoral neck z score (P = .001, r = .514), femoral neck T score (P = .002, r = .524), and lumbar spine BMD (P = .033, r = .334). No correlation was found between dual-energy x-ray absorptiometry measurements and the other variables (age, calcium, phosphorus, and alkaline phosphatase levels), and no results were reported for hepatitis C or HIV because none of the participants tested positive for those measures.

The most frequently reported causes of reduced BMD levels was vitamin D deficiency, low BMI, and low functional movement ability, although none of these was a strong independent risk factor in multivariate analysis, the authors reported.

They acknowledged that the results may not be generalizable to all patients because the study was conducted at a single center in Turkey.

“The results of our study emphasize the importance of early detection of comorbid conditions that decrease bone mass in severe hemophilia A patients,” they concluded.

The study was funded by the Yüzüncü Yıl University Scientific Research Project Committee. The authors reported no conflicts of interest.
 

SOURCE: Ekinci O et al. Haemophilia. 2019 Aug 8. doi: 10.1111/hae.13836.

Men with severe hemophilia A showed reduced levels of bone mineral density, compared with controls representative of the general population, according to findings from a case-control study.

In addition, the decrease in bone mineral density (BMD) was correlated with reduced functional ability and body mass index (BMI), and vitamin D insufficiency or deficiency.

“We aimed to investigate the presence of low BMD in adult patients diagnosed with severe hemophilia A and to evaluate the potential risk factors associated with low BMD and musculoskeletal function levels,” wrote Omer Ekinci, MD, of Firat University in Elazig, Turkey, and colleagues in Haemophilia.

The study included 41 men with severe hemophilia A and 40 men without hemophilia who were matched for age. All patients with hemophilia A received regular prophylactic therapy, and one patient had a high titre (greater than 5 Bethesda units) inhibitor against FVIII.

The researchers performed several laboratory tests: BMD was measured using dual-energy x-ray absorptiometry; BMI was recorded; and laboratory tests were performed to ascertain levels of vitamin D, calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and hepatitis C and HIV antibodies. The Functional Independence Score in Hemophilia (FISH) was used to measure functional-ability status only in the study group.

After analysis, the researchers found a significant difference between patients in the case and control groups for femoral neck and total hip BMD (P = .017 and P less than .001, respectively), but not for lumbar spine BMD (P = .071).

In patients with hemophilia aged younger than 50 years, 27.8% were found to have “low normal” BMD levels, and 19.4% showed “lower than expected” BMD levels with respect to age.

“Vitamin D insufficiency and deficiency were present in 63.4% of the patients with hemophilia, significantly higher than the control group [37.5%; P less than .001],” the researchers wrote.

There were also statistically significant positive correlations between FISH score and femoral neck BMD (P = .001, r = .530), femoral neck z score (P = .001, r = .514), femoral neck T score (P = .002, r = .524), and lumbar spine BMD (P = .033, r = .334). No correlation was found between dual-energy x-ray absorptiometry measurements and the other variables (age, calcium, phosphorus, and alkaline phosphatase levels), and no results were reported for hepatitis C or HIV because none of the participants tested positive for those measures.

The most frequently reported causes of reduced BMD levels was vitamin D deficiency, low BMI, and low functional movement ability, although none of these was a strong independent risk factor in multivariate analysis, the authors reported.

They acknowledged that the results may not be generalizable to all patients because the study was conducted at a single center in Turkey.

“The results of our study emphasize the importance of early detection of comorbid conditions that decrease bone mass in severe hemophilia A patients,” they concluded.

The study was funded by the Yüzüncü Yıl University Scientific Research Project Committee. The authors reported no conflicts of interest.
 

SOURCE: Ekinci O et al. Haemophilia. 2019 Aug 8. doi: 10.1111/hae.13836.

Men with severe hemophilia A showed reduced levels of bone mineral density, compared with controls representative of the general population, according to findings from a case-control study.

In addition, the decrease in bone mineral density (BMD) was correlated with reduced functional ability and body mass index (BMI), and vitamin D insufficiency or deficiency.

“We aimed to investigate the presence of low BMD in adult patients diagnosed with severe hemophilia A and to evaluate the potential risk factors associated with low BMD and musculoskeletal function levels,” wrote Omer Ekinci, MD, of Firat University in Elazig, Turkey, and colleagues in Haemophilia.

The study included 41 men with severe hemophilia A and 40 men without hemophilia who were matched for age. All patients with hemophilia A received regular prophylactic therapy, and one patient had a high titre (greater than 5 Bethesda units) inhibitor against FVIII.

The researchers performed several laboratory tests: BMD was measured using dual-energy x-ray absorptiometry; BMI was recorded; and laboratory tests were performed to ascertain levels of vitamin D, calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and hepatitis C and HIV antibodies. The Functional Independence Score in Hemophilia (FISH) was used to measure functional-ability status only in the study group.

After analysis, the researchers found a significant difference between patients in the case and control groups for femoral neck and total hip BMD (P = .017 and P less than .001, respectively), but not for lumbar spine BMD (P = .071).

In patients with hemophilia aged younger than 50 years, 27.8% were found to have “low normal” BMD levels, and 19.4% showed “lower than expected” BMD levels with respect to age.

“Vitamin D insufficiency and deficiency were present in 63.4% of the patients with hemophilia, significantly higher than the control group [37.5%; P less than .001],” the researchers wrote.

There were also statistically significant positive correlations between FISH score and femoral neck BMD (P = .001, r = .530), femoral neck z score (P = .001, r = .514), femoral neck T score (P = .002, r = .524), and lumbar spine BMD (P = .033, r = .334). No correlation was found between dual-energy x-ray absorptiometry measurements and the other variables (age, calcium, phosphorus, and alkaline phosphatase levels), and no results were reported for hepatitis C or HIV because none of the participants tested positive for those measures.

The most frequently reported causes of reduced BMD levels was vitamin D deficiency, low BMI, and low functional movement ability, although none of these was a strong independent risk factor in multivariate analysis, the authors reported.

They acknowledged that the results may not be generalizable to all patients because the study was conducted at a single center in Turkey.

“The results of our study emphasize the importance of early detection of comorbid conditions that decrease bone mass in severe hemophilia A patients,” they concluded.

The study was funded by the Yüzüncü Yıl University Scientific Research Project Committee. The authors reported no conflicts of interest.
 

SOURCE: Ekinci O et al. Haemophilia. 2019 Aug 8. doi: 10.1111/hae.13836.