Hematology Times

Radiation therapy could be safe as a bridging strategy for axicabtagene ciloleucel chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma, according to results from a case series.

“Effective bridging strategies may be needed to provide patients with aggressive disease access to CAR T therapy,” wrote Austin J. Sim MD, JD, of Moffitt Cancer Center in Tampa and colleagues. The findings were reported in the International Journal of Radiation Oncology, Biology, Physics.

The study included a total of 12 patients planned to receive bridging treatment with radiation prior to axicabtagene ciloleucel infusion. The cohort consisted of patients with highly aggressive disease, including six with double-hit lymphoma and six with disease 10 cm or greater in diameter.

Study participants received a radiation dose between 2 and 4 Gy per fraction to a median of 20 Gy (range, 6-36.5 Gy) and half of the participants received 20 Gy in 5 fractions or 30 Gy in 10 fractions. Of the 12 patients, 7 were administered concomitant chemotherapy.

“One patient who underwent apheresis and radiation therapy ultimately did not proceed with CAR T infusion, but was still included in our analysis,” the researchers noted.

After analysis, the researchers reported that, during bridging radiation therapy, no patients had significant toxicities or in-field disease progression of disease prior to CAR T infusion.

Post CAR T infusion, 27% of patients experienced neurotoxicity or severe cytokine release syndrome.

At 30 days, the objective response rate was 81.8%, with 27% attaining complete response. At final follow-up, the best response rate was 81.8%, with complete response achieved in 45% of patients.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, radiation dosing was not uniform and the optimal dose and fractionation remains unclear.

In addition, Dr. Sim and colleagues advised that caution should be taken if irradiation is initiated before T-cell apheresis, and if so, blood counts should be monitored closely.

“Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Atara Biotherapeutics, AstraZeneca, Celgene, GlaxoSmithKline, Novartis, Precision Biosciences, and several others.

SOURCE: Sim AJ et al. Int J Radiat Oncol Biol Phys. 2019 Jun 5. doi: 10.1016/j.ijrobp.2019.05.065.

Radiation therapy could be safe as a bridging strategy for axicabtagene ciloleucel chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma, according to results from a case series.

“Effective bridging strategies may be needed to provide patients with aggressive disease access to CAR T therapy,” wrote Austin J. Sim MD, JD, of Moffitt Cancer Center in Tampa and colleagues. The findings were reported in the International Journal of Radiation Oncology, Biology, Physics.

The study included a total of 12 patients planned to receive bridging treatment with radiation prior to axicabtagene ciloleucel infusion. The cohort consisted of patients with highly aggressive disease, including six with double-hit lymphoma and six with disease 10 cm or greater in diameter.

Study participants received a radiation dose between 2 and 4 Gy per fraction to a median of 20 Gy (range, 6-36.5 Gy) and half of the participants received 20 Gy in 5 fractions or 30 Gy in 10 fractions. Of the 12 patients, 7 were administered concomitant chemotherapy.

“One patient who underwent apheresis and radiation therapy ultimately did not proceed with CAR T infusion, but was still included in our analysis,” the researchers noted.

After analysis, the researchers reported that, during bridging radiation therapy, no patients had significant toxicities or in-field disease progression of disease prior to CAR T infusion.

Post CAR T infusion, 27% of patients experienced neurotoxicity or severe cytokine release syndrome.

At 30 days, the objective response rate was 81.8%, with 27% attaining complete response. At final follow-up, the best response rate was 81.8%, with complete response achieved in 45% of patients.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, radiation dosing was not uniform and the optimal dose and fractionation remains unclear.

In addition, Dr. Sim and colleagues advised that caution should be taken if irradiation is initiated before T-cell apheresis, and if so, blood counts should be monitored closely.

“Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Atara Biotherapeutics, AstraZeneca, Celgene, GlaxoSmithKline, Novartis, Precision Biosciences, and several others.

SOURCE: Sim AJ et al. Int J Radiat Oncol Biol Phys. 2019 Jun 5. doi: 10.1016/j.ijrobp.2019.05.065.

Radiation therapy could be safe as a bridging strategy for axicabtagene ciloleucel chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed/refractory diffuse large B-cell lymphoma, according to results from a case series.

“Effective bridging strategies may be needed to provide patients with aggressive disease access to CAR T therapy,” wrote Austin J. Sim MD, JD, of Moffitt Cancer Center in Tampa and colleagues. The findings were reported in the International Journal of Radiation Oncology, Biology, Physics.

The study included a total of 12 patients planned to receive bridging treatment with radiation prior to axicabtagene ciloleucel infusion. The cohort consisted of patients with highly aggressive disease, including six with double-hit lymphoma and six with disease 10 cm or greater in diameter.

Study participants received a radiation dose between 2 and 4 Gy per fraction to a median of 20 Gy (range, 6-36.5 Gy) and half of the participants received 20 Gy in 5 fractions or 30 Gy in 10 fractions. Of the 12 patients, 7 were administered concomitant chemotherapy.

“One patient who underwent apheresis and radiation therapy ultimately did not proceed with CAR T infusion, but was still included in our analysis,” the researchers noted.

After analysis, the researchers reported that, during bridging radiation therapy, no patients had significant toxicities or in-field disease progression of disease prior to CAR T infusion.

Post CAR T infusion, 27% of patients experienced neurotoxicity or severe cytokine release syndrome.

At 30 days, the objective response rate was 81.8%, with 27% attaining complete response. At final follow-up, the best response rate was 81.8%, with complete response achieved in 45% of patients.

The researchers acknowledged that a key limitation of the study was the retrospective design. As a result, radiation dosing was not uniform and the optimal dose and fractionation remains unclear.

In addition, Dr. Sim and colleagues advised that caution should be taken if irradiation is initiated before T-cell apheresis, and if so, blood counts should be monitored closely.

“Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy,” they concluded.

No funding sources were reported. The authors reported financial affiliations with Atara Biotherapeutics, AstraZeneca, Celgene, GlaxoSmithKline, Novartis, Precision Biosciences, and several others.

SOURCE: Sim AJ et al. Int J Radiat Oncol Biol Phys. 2019 Jun 5. doi: 10.1016/j.ijrobp.2019.05.065.

Combination polatuzumab vedotin and immunochemotherapy showed manageable safety and positive clinical outcomes in patients with previously untreated diffuse large B-cell lymphoma, according to preliminary results from a phase 1b-2 trial.

Polatuzumab vedotin has already shown single-agent activity in relapsed/refractory diffuse large B-cell lymphoma, Hervé Tilly, MD, PhD, of the University of Rouen (France), and colleagues wrote in Lancet Oncology. “We explored the combination of polatuzumab vedotin with either rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone [G-CHP].”

With respect to polatuzumab vedotin dosing, the maximum investigated dose was 1.8 mg/kg. The novel agent was infused on day 2 of cycles 1 and 2 and subsequently on day 1 of each cycle thereafter for a total of 6-8 cycles, with each cycle lasting of 21 days.

The primary outcomes of this ongoing study were treatment safety and tolerability, as well as the establishment of recommended phase 2 dosing. Secondary endpoints included overall response rate, complete response=, among others.

A total of 82 patients were included in final analysis, 25 in the phase 1b dose escalation phase and 57 in the expansion phase.

After analysis, Dr. Tilly and his colleagues reported two dose-limiting toxicities: One patient experienced a grade 4 pulmonary embolism (1.8 mg/kg plus R-CHP) and another had grade 4 febrile neutropenia and grade 3 thrombocytopenia (1.4 mg/kg plus G-CHP).

At a median follow-up of 21.5 months, the overall response rate was 89% in study participants, including 77% of patients who achieved a complete response and 12% who had a partial response.

The recommended phase 2 dose of polatuzumab vedotin was 1.8 mg/kg. At this dose, the most common grade 3 or higher toxicities were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%).

The researchers acknowledged a key limitation of the study was the nonrandomized design. As a result, dose and regimen comparisons could not be made.

The study was funded by F. Hoffmann-La Roche and Genentech. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Pfizer, and others.

SOURCE: Tilly H et al. Lancet Oncol. 2019 May 14. doi: 10.1016/S1470-2045(19)30091-9.

Combination polatuzumab vedotin and immunochemotherapy showed manageable safety and positive clinical outcomes in patients with previously untreated diffuse large B-cell lymphoma, according to preliminary results from a phase 1b-2 trial.

Polatuzumab vedotin has already shown single-agent activity in relapsed/refractory diffuse large B-cell lymphoma, Hervé Tilly, MD, PhD, of the University of Rouen (France), and colleagues wrote in Lancet Oncology. “We explored the combination of polatuzumab vedotin with either rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone [G-CHP].”

With respect to polatuzumab vedotin dosing, the maximum investigated dose was 1.8 mg/kg. The novel agent was infused on day 2 of cycles 1 and 2 and subsequently on day 1 of each cycle thereafter for a total of 6-8 cycles, with each cycle lasting of 21 days.

The primary outcomes of this ongoing study were treatment safety and tolerability, as well as the establishment of recommended phase 2 dosing. Secondary endpoints included overall response rate, complete response=, among others.

A total of 82 patients were included in final analysis, 25 in the phase 1b dose escalation phase and 57 in the expansion phase.

After analysis, Dr. Tilly and his colleagues reported two dose-limiting toxicities: One patient experienced a grade 4 pulmonary embolism (1.8 mg/kg plus R-CHP) and another had grade 4 febrile neutropenia and grade 3 thrombocytopenia (1.4 mg/kg plus G-CHP).

At a median follow-up of 21.5 months, the overall response rate was 89% in study participants, including 77% of patients who achieved a complete response and 12% who had a partial response.

The recommended phase 2 dose of polatuzumab vedotin was 1.8 mg/kg. At this dose, the most common grade 3 or higher toxicities were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%).

The researchers acknowledged a key limitation of the study was the nonrandomized design. As a result, dose and regimen comparisons could not be made.

The study was funded by F. Hoffmann-La Roche and Genentech. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Pfizer, and others.

SOURCE: Tilly H et al. Lancet Oncol. 2019 May 14. doi: 10.1016/S1470-2045(19)30091-9.

Combination polatuzumab vedotin and immunochemotherapy showed manageable safety and positive clinical outcomes in patients with previously untreated diffuse large B-cell lymphoma, according to preliminary results from a phase 1b-2 trial.

Polatuzumab vedotin has already shown single-agent activity in relapsed/refractory diffuse large B-cell lymphoma, Hervé Tilly, MD, PhD, of the University of Rouen (France), and colleagues wrote in Lancet Oncology. “We explored the combination of polatuzumab vedotin with either rituximab, cyclophosphamide, doxorubicin, and prednisone [R-CHP] or obinutuzumab, cyclophosphamide, doxorubicin, and prednisone [G-CHP].”

With respect to polatuzumab vedotin dosing, the maximum investigated dose was 1.8 mg/kg. The novel agent was infused on day 2 of cycles 1 and 2 and subsequently on day 1 of each cycle thereafter for a total of 6-8 cycles, with each cycle lasting of 21 days.

The primary outcomes of this ongoing study were treatment safety and tolerability, as well as the establishment of recommended phase 2 dosing. Secondary endpoints included overall response rate, complete response=, among others.

A total of 82 patients were included in final analysis, 25 in the phase 1b dose escalation phase and 57 in the expansion phase.

After analysis, Dr. Tilly and his colleagues reported two dose-limiting toxicities: One patient experienced a grade 4 pulmonary embolism (1.8 mg/kg plus R-CHP) and another had grade 4 febrile neutropenia and grade 3 thrombocytopenia (1.4 mg/kg plus G-CHP).

At a median follow-up of 21.5 months, the overall response rate was 89% in study participants, including 77% of patients who achieved a complete response and 12% who had a partial response.

The recommended phase 2 dose of polatuzumab vedotin was 1.8 mg/kg. At this dose, the most common grade 3 or higher toxicities were neutropenia (30%), febrile neutropenia (18%), and thrombocytopenia (9%).

The researchers acknowledged a key limitation of the study was the nonrandomized design. As a result, dose and regimen comparisons could not be made.

The study was funded by F. Hoffmann-La Roche and Genentech. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Pfizer, and others.

SOURCE: Tilly H et al. Lancet Oncol. 2019 May 14. doi: 10.1016/S1470-2045(19)30091-9.

Annual influenza vaccination rates and documentation of vaccination status appear to be suboptimal among patients with newly diagnosed diffuse large B-cell lymphoma, based on a retrospective analysis of data in the state of Georgia.

The researchers reviewed medical records of patients with a new diagnosis of diffuse large B-cell lymphoma at three Georgia hospitals. Documentation related to vaccine administration, refusal, and patient counseling was collected between Feb. 1, 2015, and Oct. 31, 2017, Andres Chang, MD, PhD, of Emory University, Atlanta, and colleagues wrote. The findings were published in Clinical Lymphoma, Myeloma & Leukemia.

Vaccination status within 1 year of diagnosis was documented for 61 of 107 patients. Among the 61 patients with documentation of influenza vaccination status, 35 (57%) were vaccinated. No reason was documented for vaccine refusal, and there was no follow-up documentation on vaccine counseling by nursing staff, physicians, or advanced practice providers in any of these admitted patients.

Nearly all documentation of influenza vaccination status came from the nursing staff. Only 4 of the 61 patients had documentation provided by primary oncologists or advanced practice providers, and those patients also had documentation from the outpatient nursing staff who subsequently administered the influenza vaccine.

“Routine outpatient vaccination screening and strategies for sharing and linking patient vaccination status between providers in different health care systems at the state and national levels could improve vaccination documentation in patients with lymphoma and provide opportunities to improve compliance,” the researchers wrote.

A key limitation of the study was the lack of adequate documentation, they explained. As a result, the reported vaccination rates were not more rigorously evaluated.

The study was funded by the Winship Cancer Institute and the National Institutes of Health. The authors reported financial affiliations with AbbVie, Acerta Pharma, Celgene, Gilead, Janssen, Pharmacyclics, and others.

SOURCE: Chang A et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.018.

Annual influenza vaccination rates and documentation of vaccination status appear to be suboptimal among patients with newly diagnosed diffuse large B-cell lymphoma, based on a retrospective analysis of data in the state of Georgia.

The researchers reviewed medical records of patients with a new diagnosis of diffuse large B-cell lymphoma at three Georgia hospitals. Documentation related to vaccine administration, refusal, and patient counseling was collected between Feb. 1, 2015, and Oct. 31, 2017, Andres Chang, MD, PhD, of Emory University, Atlanta, and colleagues wrote. The findings were published in Clinical Lymphoma, Myeloma & Leukemia.

Vaccination status within 1 year of diagnosis was documented for 61 of 107 patients. Among the 61 patients with documentation of influenza vaccination status, 35 (57%) were vaccinated. No reason was documented for vaccine refusal, and there was no follow-up documentation on vaccine counseling by nursing staff, physicians, or advanced practice providers in any of these admitted patients.

Nearly all documentation of influenza vaccination status came from the nursing staff. Only 4 of the 61 patients had documentation provided by primary oncologists or advanced practice providers, and those patients also had documentation from the outpatient nursing staff who subsequently administered the influenza vaccine.

“Routine outpatient vaccination screening and strategies for sharing and linking patient vaccination status between providers in different health care systems at the state and national levels could improve vaccination documentation in patients with lymphoma and provide opportunities to improve compliance,” the researchers wrote.

A key limitation of the study was the lack of adequate documentation, they explained. As a result, the reported vaccination rates were not more rigorously evaluated.

The study was funded by the Winship Cancer Institute and the National Institutes of Health. The authors reported financial affiliations with AbbVie, Acerta Pharma, Celgene, Gilead, Janssen, Pharmacyclics, and others.

SOURCE: Chang A et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.018.

Annual influenza vaccination rates and documentation of vaccination status appear to be suboptimal among patients with newly diagnosed diffuse large B-cell lymphoma, based on a retrospective analysis of data in the state of Georgia.

The researchers reviewed medical records of patients with a new diagnosis of diffuse large B-cell lymphoma at three Georgia hospitals. Documentation related to vaccine administration, refusal, and patient counseling was collected between Feb. 1, 2015, and Oct. 31, 2017, Andres Chang, MD, PhD, of Emory University, Atlanta, and colleagues wrote. The findings were published in Clinical Lymphoma, Myeloma & Leukemia.

Vaccination status within 1 year of diagnosis was documented for 61 of 107 patients. Among the 61 patients with documentation of influenza vaccination status, 35 (57%) were vaccinated. No reason was documented for vaccine refusal, and there was no follow-up documentation on vaccine counseling by nursing staff, physicians, or advanced practice providers in any of these admitted patients.

Nearly all documentation of influenza vaccination status came from the nursing staff. Only 4 of the 61 patients had documentation provided by primary oncologists or advanced practice providers, and those patients also had documentation from the outpatient nursing staff who subsequently administered the influenza vaccine.

“Routine outpatient vaccination screening and strategies for sharing and linking patient vaccination status between providers in different health care systems at the state and national levels could improve vaccination documentation in patients with lymphoma and provide opportunities to improve compliance,” the researchers wrote.

A key limitation of the study was the lack of adequate documentation, they explained. As a result, the reported vaccination rates were not more rigorously evaluated.

The study was funded by the Winship Cancer Institute and the National Institutes of Health. The authors reported financial affiliations with AbbVie, Acerta Pharma, Celgene, Gilead, Janssen, Pharmacyclics, and others.

SOURCE: Chang A et al. Clin Lymphoma Myeloma Leuk. 2019 Jan 2. doi: 10.1016/j.clml.2018.12.018.

The recombinant factor VIII (rFVIII) product BAY 94‐9027 had a better pharmacokinetic (PK) profile than a recombinant factor VIII-Fc fusion protein (rFVIIIFc) in patients with hemophilia A, according to a recent report.

“The objective of the current study was to directly compare the PK profiles of BAY 94-9027 and rFVIIIFc,” wrote Anita Shah, lead author and an employee of Bayer, and colleagues. The findings were published in the Annals of Hematology.

In a two-way PK crossover study, adults (aged 18-65 years) with severe hemophilia A were randomized to receive a single intravenous dose (60 IU/kg) of BAY 94-9027 or rFVIIIFc. These infusions were followed by a crossover to a single infusion of the other product.

The maximum wash-out period between infusions was 28 days, with a greater than or equal to 7-day wash-out between doses. FVIII activity was analyzed using a single one-stage clotting assay.

After population PK modeling, the median time to achieve FVIII threshold levels (1 IU/dL) was found to be 13 hours longer for BAY 94-9027 than it was for rFVIIIFc following a single intravenous dose of 60 IU/kg.

In addition, the team reported that the geometric mean area under the curve from baseline to the last data point was significantly greater for BAY 94-9027 than it was for rFVIIIFc (coefficient of variation, 2,940 vs. 2,360 IU h/dL; P = .0001)

“This increase in the time above threshold may thereby provide improved bleeding protection,” the authors explained.

With respect to safety, no adverse events were reported among study participants.

The researchers acknowledged a key limitation of the study was the nonexistence of a two-stage chromogenic assay to measure FVIII activity of both products. As a result, a one-stage clotting assay was used to analyze FVIII activity for both treatments.

“Real-world data may provide an insight into whether these PK advantages provide additional bleeding protection,” they concluded.

The study was funded by Bayer AG. The authors reported financial affiliations with Bayer, LFB, Octapharma, Pfizer, Roche, Shire, and several others.

SOURCE: Shah A et al. Ann Hematol. 2019 Jun 24. doi: 10.1007/s00277-019-03747-2.

The recombinant factor VIII (rFVIII) product BAY 94‐9027 had a better pharmacokinetic (PK) profile than a recombinant factor VIII-Fc fusion protein (rFVIIIFc) in patients with hemophilia A, according to a recent report.

“The objective of the current study was to directly compare the PK profiles of BAY 94-9027 and rFVIIIFc,” wrote Anita Shah, lead author and an employee of Bayer, and colleagues. The findings were published in the Annals of Hematology.

In a two-way PK crossover study, adults (aged 18-65 years) with severe hemophilia A were randomized to receive a single intravenous dose (60 IU/kg) of BAY 94-9027 or rFVIIIFc. These infusions were followed by a crossover to a single infusion of the other product.

The maximum wash-out period between infusions was 28 days, with a greater than or equal to 7-day wash-out between doses. FVIII activity was analyzed using a single one-stage clotting assay.

After population PK modeling, the median time to achieve FVIII threshold levels (1 IU/dL) was found to be 13 hours longer for BAY 94-9027 than it was for rFVIIIFc following a single intravenous dose of 60 IU/kg.

In addition, the team reported that the geometric mean area under the curve from baseline to the last data point was significantly greater for BAY 94-9027 than it was for rFVIIIFc (coefficient of variation, 2,940 vs. 2,360 IU h/dL; P = .0001)

“This increase in the time above threshold may thereby provide improved bleeding protection,” the authors explained.

With respect to safety, no adverse events were reported among study participants.

The researchers acknowledged a key limitation of the study was the nonexistence of a two-stage chromogenic assay to measure FVIII activity of both products. As a result, a one-stage clotting assay was used to analyze FVIII activity for both treatments.

“Real-world data may provide an insight into whether these PK advantages provide additional bleeding protection,” they concluded.

The study was funded by Bayer AG. The authors reported financial affiliations with Bayer, LFB, Octapharma, Pfizer, Roche, Shire, and several others.

SOURCE: Shah A et al. Ann Hematol. 2019 Jun 24. doi: 10.1007/s00277-019-03747-2.

The recombinant factor VIII (rFVIII) product BAY 94‐9027 had a better pharmacokinetic (PK) profile than a recombinant factor VIII-Fc fusion protein (rFVIIIFc) in patients with hemophilia A, according to a recent report.

“The objective of the current study was to directly compare the PK profiles of BAY 94-9027 and rFVIIIFc,” wrote Anita Shah, lead author and an employee of Bayer, and colleagues. The findings were published in the Annals of Hematology.

In a two-way PK crossover study, adults (aged 18-65 years) with severe hemophilia A were randomized to receive a single intravenous dose (60 IU/kg) of BAY 94-9027 or rFVIIIFc. These infusions were followed by a crossover to a single infusion of the other product.

The maximum wash-out period between infusions was 28 days, with a greater than or equal to 7-day wash-out between doses. FVIII activity was analyzed using a single one-stage clotting assay.

After population PK modeling, the median time to achieve FVIII threshold levels (1 IU/dL) was found to be 13 hours longer for BAY 94-9027 than it was for rFVIIIFc following a single intravenous dose of 60 IU/kg.

In addition, the team reported that the geometric mean area under the curve from baseline to the last data point was significantly greater for BAY 94-9027 than it was for rFVIIIFc (coefficient of variation, 2,940 vs. 2,360 IU h/dL; P = .0001)

“This increase in the time above threshold may thereby provide improved bleeding protection,” the authors explained.

With respect to safety, no adverse events were reported among study participants.

The researchers acknowledged a key limitation of the study was the nonexistence of a two-stage chromogenic assay to measure FVIII activity of both products. As a result, a one-stage clotting assay was used to analyze FVIII activity for both treatments.

“Real-world data may provide an insight into whether these PK advantages provide additional bleeding protection,” they concluded.

The study was funded by Bayer AG. The authors reported financial affiliations with Bayer, LFB, Octapharma, Pfizer, Roche, Shire, and several others.

SOURCE: Shah A et al. Ann Hematol. 2019 Jun 24. doi: 10.1007/s00277-019-03747-2.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, Fla. – A study of sickle cell patients at a clinic in the Bronx found that upwards of 75% of them get a prescription for hydroxyurea to improve hemoglobin levels, but that one-third have discontinued use for various reasons, according to results reported at the 13^th annual Foundation for Sickle Cell Disease Research symposium here.

“The results identify variability in reported side effects and reasons for discontinuation, and highlight the importance of clear communication between providers and patients to discuss the benefits and challenges of hydroxyurea,” said Caterina Minniti, MD, professor of clinical medicine and pediatrics at Einstein College of Medicine and director of the Sickle Cell Center for Adults at Montefiore Hospital, Bronx, N.Y. The study analyzed self-reporting surveys completed by 224 adult outpatients in the Montefiore sickle cell clinic, and then verified the data in the electronic medical record, Dr. Minniti said. She noted, “Our population is unique in the Bronx in that we have a high percentage of Hispanic patients.” They comprised 24.1% of the study population.

“We found that 77.2% of the patients have ever been prescribed hydroxyurea,” she said. “That was really great.” Also, 91% of those with severe genotypes of SCD had been prescribed the drug; 68% of them were still taking hydroxyurea at the time of the survey, she said. Among patients with the mild genotype, 42.1% had been prescribed hydroxyurea and half were still on it when they completed their surveys.

When the survey evaluated how long patients had been taking the drug, she said, “That’s where I start to get concerned.” About half – 48.6% – had taken the drug for one to five years, “which is a very short period of time,” Dr. Minniti said. Another 15% were on hydroxyurea for less than a year, 23% for 5 to 10 years and 19% for 10 years or more.

The study drilled down into reasons why patients discontinued the drug. Side effects were cited by 24.6% (n=15). They include fatigue, hair loss, and GI upset. Other reasons include perceived ineffectiveness (16.4%, n=10); physician direction (14.8%, n=9), and reproductive health and ulcer formation (each at 8.2%, n=5).

“Many patients perceive ineffectiveness of hydroxyurea in the short term, but the benefits of hydoxyurea stem from chronic use over the long term,” Dr. Minniti said. She noted that some patients discontinued the drug for legitimate medical indications, “such as pregnancy and breast feeding, but were not restarted afterward.”

Dr. Minniti disclosed relationships with Novartis, Global Blood Therapeutics, Teutona, Bluebird Bio, GBT and Bayer.

SOURCE: Minniti C, et al. Abstract no. JSCDH-D-19-00058. Foundation for Sickle Cell Disease Research Symposium; Fort Lauderdale, Fla.; June 9, 2019.

FORT LAUDERDALE, FLA. – Hip joint pain and deterioration can be a painful and disabling outcome for patients with sickle cell disease, but femoral head core decompression with the addition of bone marrow aspirate concentrate decreases their pain and may help avoid or delay hip replacement, according to results of a pilot study presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

Eric Fornari, MD, of the Children’s Hospital at Montefiore in Bronx, N.Y., reported on results of core decompression (CD) in 35 hips of 26 sickle cell patients; 17 underwent CD only and 18 had CD with injection of bone marrow aspirate concentrate (CD+BMAC). The average patient age was 24.3 years, with a range from 9.7-50.7 years.

“Compared to patients treated with CD alone, patients treated with CD+BMAC complained of significantly less pain and had significant improvement in their functional scores and patient-related outcomes at short-term follow-up,” Dr. Fornari said.

Among the CD+BMAC patients, pain scores declined two points on average, from 6 preoperatively to 4 postoperatively, he said. This was clinically significant, compared with the CD-only group, Dr. Fornari said.

Patients in the CD+BMAC group also reported consistently superior hip outcome and modified Harris hip scores. With either treatment, more than 90% of patients were pain-free and walked independently at their most recent follow-up, he said.

The objective of CD is to relieve pressure within the head of the femur, stimulate vascularity and target the avascular necrosis (AVN) lesion within the head that is visible on imaging. To get the bone marrow aspirate concentrate, Dr. Fornari extracts 120 cc of bone marrow from the iliac crest, then concentrates it to 12 cc. The same instrument is used to tap into the femoral head and inject the bone marrow aspirate concentrate. The study looked at clinical and radiographic outcomes of treated patients.

Average follow-up for the entire study population was 3.6 years, but that varied widely between the two groups (CD-only at almost 6 years, CD+BMAC at 1.4 years) because CD+BMAC has only been done for the last 3 years, Dr. Fornari said.

Progression to total hip arthroplasty (THA) was similar between both groups: 5 of 17 patients (29%) for CD-only vs. 4 of 18 patients (22%) for CD+BMAC (P = .711).

“When you look at progression, there were a number of hips that got CD or CD+BMAC and were better postoperatively; they went from a Ficat score of stage II to a stage I, or stage III to stage II,” he said.

X-rays were not always a reliable marker of outcome after either CD procedure, Dr. Fornari noted. “I’ve seen patients who’ve had terrible looking X-rays who have no pain, and patients who have totally normal X-rays that are completely debilitated,” he said. “We have to start asking ourselves, ‘What is the marker of success?’ because when we do this patients are feeling better.”

Multivariate analysis was used to identify factors predictive of progression to THA after the procedure, Dr. Fornari said. “Age of diagnosis, age of surgery, female gender, and lower hydroxyurea dose at surgery were predictive of advancing disease, whereas a higher dose of hydroxyurea was predictive against advancement,” he said.

The average age of patients who had no THA after either procedure was 21 years, compared with 33.9 years for those who had THA (P = .003). Average hydroxyurea dose at surgery was 24.7 mg/kg in the no-THA group vs. 12.5 mg/kg in those who had THA (P = .005).

Notably, there were no readmissions, fractures, deep vein thromboses, pulmonary embolisms or infarctions after CD, Dr. Fornari said. Transfusions were required in two CD-only and three CD+BMAC patients. Hospitalization rates for vaso-occlusive crisis were similar between groups (P = .103).

Dr. Fornari said the challenge is to identify suitable patients for these procedures. “These are complicated patients and you don’t want to put them through the process of having surgery, putting them on crutches and restricted weight bearing, if they’re not going to get better,” he said. “This procedure done minimally invasively is not the end all and be all, but we have to figure out who are the right patients for it. Patient selection is key.”

Finding those patients starts with a rigorous history and physical exam, he said. Physicians should have a “low threshold” for MRI in these patients because that will reveal findings, such as pre-collapse disease and characteristic of AVN lesions, that may appear normal on X-ray. Patient education is also important. “To think that an injection into the top of the hip is going to solve all their problems is a little naive, so you have to have an honest conversation with the patient,” he said.

Dr. Fornari reported having no financial disclosures.

SOURCE: Fornari ED et al. FSCDR 2019, Abstract JSCDH-D-19-00004.

FORT LAUDERDALE, FLA. – Hip joint pain and deterioration can be a painful and disabling outcome for patients with sickle cell disease, but femoral head core decompression with the addition of bone marrow aspirate concentrate decreases their pain and may help avoid or delay hip replacement, according to results of a pilot study presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

Eric Fornari, MD, of the Children’s Hospital at Montefiore in Bronx, N.Y., reported on results of core decompression (CD) in 35 hips of 26 sickle cell patients; 17 underwent CD only and 18 had CD with injection of bone marrow aspirate concentrate (CD+BMAC). The average patient age was 24.3 years, with a range from 9.7-50.7 years.

“Compared to patients treated with CD alone, patients treated with CD+BMAC complained of significantly less pain and had significant improvement in their functional scores and patient-related outcomes at short-term follow-up,” Dr. Fornari said.

Among the CD+BMAC patients, pain scores declined two points on average, from 6 preoperatively to 4 postoperatively, he said. This was clinically significant, compared with the CD-only group, Dr. Fornari said.

Patients in the CD+BMAC group also reported consistently superior hip outcome and modified Harris hip scores. With either treatment, more than 90% of patients were pain-free and walked independently at their most recent follow-up, he said.

The objective of CD is to relieve pressure within the head of the femur, stimulate vascularity and target the avascular necrosis (AVN) lesion within the head that is visible on imaging. To get the bone marrow aspirate concentrate, Dr. Fornari extracts 120 cc of bone marrow from the iliac crest, then concentrates it to 12 cc. The same instrument is used to tap into the femoral head and inject the bone marrow aspirate concentrate. The study looked at clinical and radiographic outcomes of treated patients.

Average follow-up for the entire study population was 3.6 years, but that varied widely between the two groups (CD-only at almost 6 years, CD+BMAC at 1.4 years) because CD+BMAC has only been done for the last 3 years, Dr. Fornari said.

Progression to total hip arthroplasty (THA) was similar between both groups: 5 of 17 patients (29%) for CD-only vs. 4 of 18 patients (22%) for CD+BMAC (P = .711).

“When you look at progression, there were a number of hips that got CD or CD+BMAC and were better postoperatively; they went from a Ficat score of stage II to a stage I, or stage III to stage II,” he said.

X-rays were not always a reliable marker of outcome after either CD procedure, Dr. Fornari noted. “I’ve seen patients who’ve had terrible looking X-rays who have no pain, and patients who have totally normal X-rays that are completely debilitated,” he said. “We have to start asking ourselves, ‘What is the marker of success?’ because when we do this patients are feeling better.”

Multivariate analysis was used to identify factors predictive of progression to THA after the procedure, Dr. Fornari said. “Age of diagnosis, age of surgery, female gender, and lower hydroxyurea dose at surgery were predictive of advancing disease, whereas a higher dose of hydroxyurea was predictive against advancement,” he said.

The average age of patients who had no THA after either procedure was 21 years, compared with 33.9 years for those who had THA (P = .003). Average hydroxyurea dose at surgery was 24.7 mg/kg in the no-THA group vs. 12.5 mg/kg in those who had THA (P = .005).

Notably, there were no readmissions, fractures, deep vein thromboses, pulmonary embolisms or infarctions after CD, Dr. Fornari said. Transfusions were required in two CD-only and three CD+BMAC patients. Hospitalization rates for vaso-occlusive crisis were similar between groups (P = .103).

Dr. Fornari said the challenge is to identify suitable patients for these procedures. “These are complicated patients and you don’t want to put them through the process of having surgery, putting them on crutches and restricted weight bearing, if they’re not going to get better,” he said. “This procedure done minimally invasively is not the end all and be all, but we have to figure out who are the right patients for it. Patient selection is key.”

Finding those patients starts with a rigorous history and physical exam, he said. Physicians should have a “low threshold” for MRI in these patients because that will reveal findings, such as pre-collapse disease and characteristic of AVN lesions, that may appear normal on X-ray. Patient education is also important. “To think that an injection into the top of the hip is going to solve all their problems is a little naive, so you have to have an honest conversation with the patient,” he said.

Dr. Fornari reported having no financial disclosures.

SOURCE: Fornari ED et al. FSCDR 2019, Abstract JSCDH-D-19-00004.

FORT LAUDERDALE, FLA. – Hip joint pain and deterioration can be a painful and disabling outcome for patients with sickle cell disease, but femoral head core decompression with the addition of bone marrow aspirate concentrate decreases their pain and may help avoid or delay hip replacement, according to results of a pilot study presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

Eric Fornari, MD, of the Children’s Hospital at Montefiore in Bronx, N.Y., reported on results of core decompression (CD) in 35 hips of 26 sickle cell patients; 17 underwent CD only and 18 had CD with injection of bone marrow aspirate concentrate (CD+BMAC). The average patient age was 24.3 years, with a range from 9.7-50.7 years.

“Compared to patients treated with CD alone, patients treated with CD+BMAC complained of significantly less pain and had significant improvement in their functional scores and patient-related outcomes at short-term follow-up,” Dr. Fornari said.

Among the CD+BMAC patients, pain scores declined two points on average, from 6 preoperatively to 4 postoperatively, he said. This was clinically significant, compared with the CD-only group, Dr. Fornari said.

Patients in the CD+BMAC group also reported consistently superior hip outcome and modified Harris hip scores. With either treatment, more than 90% of patients were pain-free and walked independently at their most recent follow-up, he said.

The objective of CD is to relieve pressure within the head of the femur, stimulate vascularity and target the avascular necrosis (AVN) lesion within the head that is visible on imaging. To get the bone marrow aspirate concentrate, Dr. Fornari extracts 120 cc of bone marrow from the iliac crest, then concentrates it to 12 cc. The same instrument is used to tap into the femoral head and inject the bone marrow aspirate concentrate. The study looked at clinical and radiographic outcomes of treated patients.

Average follow-up for the entire study population was 3.6 years, but that varied widely between the two groups (CD-only at almost 6 years, CD+BMAC at 1.4 years) because CD+BMAC has only been done for the last 3 years, Dr. Fornari said.

Progression to total hip arthroplasty (THA) was similar between both groups: 5 of 17 patients (29%) for CD-only vs. 4 of 18 patients (22%) for CD+BMAC (P = .711).

“When you look at progression, there were a number of hips that got CD or CD+BMAC and were better postoperatively; they went from a Ficat score of stage II to a stage I, or stage III to stage II,” he said.

X-rays were not always a reliable marker of outcome after either CD procedure, Dr. Fornari noted. “I’ve seen patients who’ve had terrible looking X-rays who have no pain, and patients who have totally normal X-rays that are completely debilitated,” he said. “We have to start asking ourselves, ‘What is the marker of success?’ because when we do this patients are feeling better.”

Multivariate analysis was used to identify factors predictive of progression to THA after the procedure, Dr. Fornari said. “Age of diagnosis, age of surgery, female gender, and lower hydroxyurea dose at surgery were predictive of advancing disease, whereas a higher dose of hydroxyurea was predictive against advancement,” he said.

The average age of patients who had no THA after either procedure was 21 years, compared with 33.9 years for those who had THA (P = .003). Average hydroxyurea dose at surgery was 24.7 mg/kg in the no-THA group vs. 12.5 mg/kg in those who had THA (P = .005).

Notably, there were no readmissions, fractures, deep vein thromboses, pulmonary embolisms or infarctions after CD, Dr. Fornari said. Transfusions were required in two CD-only and three CD+BMAC patients. Hospitalization rates for vaso-occlusive crisis were similar between groups (P = .103).

Dr. Fornari said the challenge is to identify suitable patients for these procedures. “These are complicated patients and you don’t want to put them through the process of having surgery, putting them on crutches and restricted weight bearing, if they’re not going to get better,” he said. “This procedure done minimally invasively is not the end all and be all, but we have to figure out who are the right patients for it. Patient selection is key.”

Finding those patients starts with a rigorous history and physical exam, he said. Physicians should have a “low threshold” for MRI in these patients because that will reveal findings, such as pre-collapse disease and characteristic of AVN lesions, that may appear normal on X-ray. Patient education is also important. “To think that an injection into the top of the hip is going to solve all their problems is a little naive, so you have to have an honest conversation with the patient,” he said.

Dr. Fornari reported having no financial disclosures.

SOURCE: Fornari ED et al. FSCDR 2019, Abstract JSCDH-D-19-00004.

Janssen’s daratumumab (Darzalex) has picked up a sixth adult multiple myeloma indication, this time in combination with lenalidomide (Revlimid) and dexamethasone in newly diagnosed patients ineligible for autologous stem cell transplants.

The phase 3 MAIA trial found that 97 of 368 patients (26.4%) treated with the combination – dubbed DRd – progressed or died at a median follow-up of 28 months, versus 143 of 269 (38.8%) treated with lenalidomide and dexamethasone alone (Rd). An estimated 55.6% of patients on lenalidomide and dexamethasone, versus 70.6% with the daratumumab add-on, were alive without progression at 30 months (N Engl J Med. 2019 May 30;380[22]:2104-15).


Previously approved indications for daratumumab include relapsed or refractory disease after at least one other therapy; and combination treatment with bortezomib, melphalan, and prednisone, also in newly diagnosed patients who are ineligible for transplant.

The most common grade 3 and 4 adverse events reported in the MAIA trial were neutropenia (50.0% for the DRd group versus 35.3% for the Rd group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).

aotto@mdedge.com

Janssen’s daratumumab (Darzalex) has picked up a sixth adult multiple myeloma indication, this time in combination with lenalidomide (Revlimid) and dexamethasone in newly diagnosed patients ineligible for autologous stem cell transplants.

The phase 3 MAIA trial found that 97 of 368 patients (26.4%) treated with the combination – dubbed DRd – progressed or died at a median follow-up of 28 months, versus 143 of 269 (38.8%) treated with lenalidomide and dexamethasone alone (Rd). An estimated 55.6% of patients on lenalidomide and dexamethasone, versus 70.6% with the daratumumab add-on, were alive without progression at 30 months (N Engl J Med. 2019 May 30;380[22]:2104-15).


Previously approved indications for daratumumab include relapsed or refractory disease after at least one other therapy; and combination treatment with bortezomib, melphalan, and prednisone, also in newly diagnosed patients who are ineligible for transplant.

The most common grade 3 and 4 adverse events reported in the MAIA trial were neutropenia (50.0% for the DRd group versus 35.3% for the Rd group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).

aotto@mdedge.com

Janssen’s daratumumab (Darzalex) has picked up a sixth adult multiple myeloma indication, this time in combination with lenalidomide (Revlimid) and dexamethasone in newly diagnosed patients ineligible for autologous stem cell transplants.

The phase 3 MAIA trial found that 97 of 368 patients (26.4%) treated with the combination – dubbed DRd – progressed or died at a median follow-up of 28 months, versus 143 of 269 (38.8%) treated with lenalidomide and dexamethasone alone (Rd). An estimated 55.6% of patients on lenalidomide and dexamethasone, versus 70.6% with the daratumumab add-on, were alive without progression at 30 months (N Engl J Med. 2019 May 30;380[22]:2104-15).


Previously approved indications for daratumumab include relapsed or refractory disease after at least one other therapy; and combination treatment with bortezomib, melphalan, and prednisone, also in newly diagnosed patients who are ineligible for transplant.

The most common grade 3 and 4 adverse events reported in the MAIA trial were neutropenia (50.0% for the DRd group versus 35.3% for the Rd group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).

aotto@mdedge.com

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

lfranki@mdedge.com

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

lfranki@mdedge.com

The Food and Drug Administration has approved a supplemental New Drug Application expanding the indication of avatrombopag (Doptelet) to include treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to previous therapy, according to Dova Pharmaceuticals.

Olivier Le Moal/Getty Images

FDA approval was based on results of a phase 3 trial in which a majority of patients who received avatrombopag achieved a platelet count of at least 50,000 per mcg after 8 days of therapy. In addition, efficacy was superior to patients in the placebo group in the maintenance of platelet counts during the 6-month treatment period.

Avatrombopag – an oral, thrombopoietin receptor agonist administered with food – was previously indicated for the treatment of chronic liver disease in adult patients who are scheduled to undergo a procedure. The most common adverse reactions in patients with ITP include headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Find the full press release on the Dova Pharmaceuticals website.

lfranki@mdedge.com

AMSTERDAM – For patients with FLT3-mutated, relapsed or refractory acute myeloid leukemia (AML), gilteritinib (Xospata) offers better median overall survival than salvage chemotherapy, according to results from the phase 3 ADMIRAL trial.

Patients treated with gilteritinib also more often responded to therapy and entered remission, reported lead author Alexander Perl, MD, of the University of Pennsylvania, Philadelphia.

To overcome resistance mechanisms to existing FLT3 inhibitors, drug developers have been seeking agents with activity against both FLT3-ITD and FLT3-TKD mutations, Dr. Perl explained during his presentation at the annual congress of the European Hematology Association. “Gilteritinib is one of these agents,” he said, noting a unique mechanism of action that also may limit toxicity concerns associated with existing FLT3 inhibitors.

The international ADMIRAL trial involved 371 patients with FLT3-mutated AML who had not responded to induction therapy or were untreated after first relapse.

The population was randomized in a 2:1 ratio to receive either gilteritinib 120 mg/day or one of four salvage chemotherapy regimens: azacitidine (AZA), low-dose cytarabine (LoDAC), mitoxantrone/etoposide/cytarabine (MEC), or fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA).

Coprimary endpoints were overall survival and the combined rate of complete remission and complete remission with partial hematologic recovery (CR/CRh). Secondary endpoints were complete remission rate and event-free survival.

Demographic data showed that the median patient age was 62 years with a broad range (19-85 years). Most patients were positive for FLT3-ITD (88.4%), while fewer tested positive for FLT3-TKD (8.4%) or both mutations (1.9%). Relapsed AML was more common than refractory disease (60.6% vs. 39.4%).

The efficacy analysis revealed that patients treated with gilteritinib had a median overall survival of 9.3 months, significantly longer than the 5.6 months among those treated with salvage chemotherapy (hazard ratio for death = 0.637; P = .0007). The 1-year survival rate was 37.1% for the gilteritinib group, compared with 16.7% among those who received chemotherapy.

The superiority of gilteritinib was further supported by twofold higher rates of CR/CRh (34.0% vs. 15.3%) and complete remission (21.1% vs. 10.5%). Similarly, median event-free survival was significantly longer in the gilteritinib group (2.8 vs. 0.7 months). Most subgroups, such as age and sex, showed consistent benefit.

Overall, gilteritinib demonstrated a favorable safety profile. After adjusting for exposure duration, serious treatment related adverse events were more common in the chemotherapy group than the gilteritinib group (9.2% vs. 7.1%). Common grade 3 or higher adverse events related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).

“We were able to give [gilteritinib] in an outpatient setting,” Dr. Perl said.

Although comparisons between responses based on mutation type were not possible, owing to small sample sizes, Dr. Perl highlighted that gilteritinib showed activity against both FLT3 mutation subtypes.

“This drug has been approved on the results of this study,” Dr. Perl said. “Because of this, we have a new standard of care for this population.”

The study was funded by Astellas. The investigators reported financial relationships with AbbVie, Bayer, Takeda, and other companies.

SOURCE: Perl A et al. EHA Congress, Abstract S876.

AMSTERDAM – For patients with FLT3-mutated, relapsed or refractory acute myeloid leukemia (AML), gilteritinib (Xospata) offers better median overall survival than salvage chemotherapy, according to results from the phase 3 ADMIRAL trial.

Patients treated with gilteritinib also more often responded to therapy and entered remission, reported lead author Alexander Perl, MD, of the University of Pennsylvania, Philadelphia.

To overcome resistance mechanisms to existing FLT3 inhibitors, drug developers have been seeking agents with activity against both FLT3-ITD and FLT3-TKD mutations, Dr. Perl explained during his presentation at the annual congress of the European Hematology Association. “Gilteritinib is one of these agents,” he said, noting a unique mechanism of action that also may limit toxicity concerns associated with existing FLT3 inhibitors.

The international ADMIRAL trial involved 371 patients with FLT3-mutated AML who had not responded to induction therapy or were untreated after first relapse.

The population was randomized in a 2:1 ratio to receive either gilteritinib 120 mg/day or one of four salvage chemotherapy regimens: azacitidine (AZA), low-dose cytarabine (LoDAC), mitoxantrone/etoposide/cytarabine (MEC), or fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA).

Coprimary endpoints were overall survival and the combined rate of complete remission and complete remission with partial hematologic recovery (CR/CRh). Secondary endpoints were complete remission rate and event-free survival.

Demographic data showed that the median patient age was 62 years with a broad range (19-85 years). Most patients were positive for FLT3-ITD (88.4%), while fewer tested positive for FLT3-TKD (8.4%) or both mutations (1.9%). Relapsed AML was more common than refractory disease (60.6% vs. 39.4%).

The efficacy analysis revealed that patients treated with gilteritinib had a median overall survival of 9.3 months, significantly longer than the 5.6 months among those treated with salvage chemotherapy (hazard ratio for death = 0.637; P = .0007). The 1-year survival rate was 37.1% for the gilteritinib group, compared with 16.7% among those who received chemotherapy.

The superiority of gilteritinib was further supported by twofold higher rates of CR/CRh (34.0% vs. 15.3%) and complete remission (21.1% vs. 10.5%). Similarly, median event-free survival was significantly longer in the gilteritinib group (2.8 vs. 0.7 months). Most subgroups, such as age and sex, showed consistent benefit.

Overall, gilteritinib demonstrated a favorable safety profile. After adjusting for exposure duration, serious treatment related adverse events were more common in the chemotherapy group than the gilteritinib group (9.2% vs. 7.1%). Common grade 3 or higher adverse events related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).

“We were able to give [gilteritinib] in an outpatient setting,” Dr. Perl said.

Although comparisons between responses based on mutation type were not possible, owing to small sample sizes, Dr. Perl highlighted that gilteritinib showed activity against both FLT3 mutation subtypes.

“This drug has been approved on the results of this study,” Dr. Perl said. “Because of this, we have a new standard of care for this population.”

The study was funded by Astellas. The investigators reported financial relationships with AbbVie, Bayer, Takeda, and other companies.

SOURCE: Perl A et al. EHA Congress, Abstract S876.

AMSTERDAM – For patients with FLT3-mutated, relapsed or refractory acute myeloid leukemia (AML), gilteritinib (Xospata) offers better median overall survival than salvage chemotherapy, according to results from the phase 3 ADMIRAL trial.

Patients treated with gilteritinib also more often responded to therapy and entered remission, reported lead author Alexander Perl, MD, of the University of Pennsylvania, Philadelphia.

To overcome resistance mechanisms to existing FLT3 inhibitors, drug developers have been seeking agents with activity against both FLT3-ITD and FLT3-TKD mutations, Dr. Perl explained during his presentation at the annual congress of the European Hematology Association. “Gilteritinib is one of these agents,” he said, noting a unique mechanism of action that also may limit toxicity concerns associated with existing FLT3 inhibitors.

The international ADMIRAL trial involved 371 patients with FLT3-mutated AML who had not responded to induction therapy or were untreated after first relapse.

The population was randomized in a 2:1 ratio to receive either gilteritinib 120 mg/day or one of four salvage chemotherapy regimens: azacitidine (AZA), low-dose cytarabine (LoDAC), mitoxantrone/etoposide/cytarabine (MEC), or fludarabine/cytarabine/granulocyte colony-stimulating factor/idarubicin (FLAG-IDA).

Coprimary endpoints were overall survival and the combined rate of complete remission and complete remission with partial hematologic recovery (CR/CRh). Secondary endpoints were complete remission rate and event-free survival.

Demographic data showed that the median patient age was 62 years with a broad range (19-85 years). Most patients were positive for FLT3-ITD (88.4%), while fewer tested positive for FLT3-TKD (8.4%) or both mutations (1.9%). Relapsed AML was more common than refractory disease (60.6% vs. 39.4%).

The efficacy analysis revealed that patients treated with gilteritinib had a median overall survival of 9.3 months, significantly longer than the 5.6 months among those treated with salvage chemotherapy (hazard ratio for death = 0.637; P = .0007). The 1-year survival rate was 37.1% for the gilteritinib group, compared with 16.7% among those who received chemotherapy.

The superiority of gilteritinib was further supported by twofold higher rates of CR/CRh (34.0% vs. 15.3%) and complete remission (21.1% vs. 10.5%). Similarly, median event-free survival was significantly longer in the gilteritinib group (2.8 vs. 0.7 months). Most subgroups, such as age and sex, showed consistent benefit.

Overall, gilteritinib demonstrated a favorable safety profile. After adjusting for exposure duration, serious treatment related adverse events were more common in the chemotherapy group than the gilteritinib group (9.2% vs. 7.1%). Common grade 3 or higher adverse events related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%).

“We were able to give [gilteritinib] in an outpatient setting,” Dr. Perl said.

Although comparisons between responses based on mutation type were not possible, owing to small sample sizes, Dr. Perl highlighted that gilteritinib showed activity against both FLT3 mutation subtypes.

“This drug has been approved on the results of this study,” Dr. Perl said. “Because of this, we have a new standard of care for this population.”

The study was funded by Astellas. The investigators reported financial relationships with AbbVie, Bayer, Takeda, and other companies.

SOURCE: Perl A et al. EHA Congress, Abstract S876.

FORT LAUDERDALE, FLA. – Orthopedic crises are common in patients with sickle cell disease, ranging from osteonecrosis to bone infarction, and physicians who manage these patients should know how to recognize these crises and not hesitate to consult an orthopedic surgeon early on, according to one expert at the annual meeting of the Foundation for Sickle Cell Disease Research.

Richard Mark Kirkner/MDedge News

“Sickle cell is a common entity in orthopedic surgery, so you shouldn’t hesitate in the hospital or outpatient settings to call for an orthopedic surgeon when you’re dealing with acute pain crises, medullary infarcts, and osteonecrosis,” said Mark W. Bridges, MD, an orthopedic surgeon with Orthopaedic Associates in Southern Florida.

Dr. Bridges noted that the femoral head is the most common location for osteonecrosis, one of the four major orthopedic manifestations of sickle cell disease that he reviewed. The others are septic arthritis, osteomyelitis, and bone infarction.

“Bone infarction is more common than osteomyelitis, and gadolinium-enhanced MRI can help to differentiate the two,” he said.

Osteonecrosis occurs when ischemic cells die, weakening the subchondral bone. Besides the femoral head, osteonecrosis commonly affects the humeral head of the shoulder and the femoral condyles of the knee. Dr. Bridges reviewed the five stages of the Ficat and Arlet classification of osteonecrosis:

• 0 – no pain, normal x-rays.
• I – pain, normal x-rays but abnormal MRI.
• II – pain, abnormal x-ray (sclerosis without collapse).
• III – pain (subchondral collapse without joint degeneration).
• IV – pain (arthritic changes with subchondral collapse).

For osteonecrosis of the shoulder, Dr. Bridges said four surgical options exist: core decompression for stages I and II; humeral head resurfacing for stages II and III; and hemiarthroplasty or total shoulder replacement for stages III and IV.

“No medical therapies are known to slow the progression,” he said.

Total joint replacement can be inevitable in these patients when total collapse of the joint occurs, but Dr. Bridges added a word of caution. “Overall when it comes down to replacing joints, there are more complications in patients that have [sickle cell disease],” he said. “Normally the complication rate is about 1%; that typically goes up to about 10% in SCD patients, but when you have a patient with end-stage disease – shoulder collapse or hip collapse – you have to do something.”

Septic arthritis is an infection within the joint space, most commonly the hip, and it affects 5% of children and 0.3% of adults with sickle cell disease (Clin Orthop Relat Res. 2010;468:1676-81).

“This is very similar to a vaso-occlusive crisis,” Dr. Bridges said.

MRI with gadolinium can help guide treatment, and blood cultures and joint aspiration can identify the infectious microbe. Staphylococcus aureus is the most common, Dr. Bridges said. Treatment consists of IV antibiotics, irrigation, and debridement.

Osteomyelitis is an infection within the bone with symptoms similar to those of septic arthritis, although osteomyelitis patients are typically sicker, he said. MRI with gadolinium is indicated in patients who don’t respond to IV fluid, oxygenation, and nonsteroidal anti-inflammatory drugs. “Try to treat them like they have vaso-occlusive crisis,” he said. Blood cultures usually suffice in these patients; bone aspiration is rarely needed, Dr. Bridges said.

The most common organisms are Staphylococcus aureus and Salmonella, and sickle cell disease patients can have infections in more than one location, Dr. Bridges noted.

“If IV antibiotics don’t work, then these patients need surgical debridement,” he added.

Adults are prone to a higher rate of complications than are children, including joint stiffness, osteonecrosis, pathologic fracture, and chronic osteomyelitis.

Ischemic marrow from vaso-occlusion can result in bone infarction. With its severe pain, swelling, erythema, and loss of motion, bone infarction can appear similar to osteomyelitis and septic arthritis, although a high-grade fever is uncommon in bone infarction. Unlike osteomyelitis, gadolinium on MRI does not enhance in bone infarction.

Treatment “consists of supportive management with pain medications, hydration, and antibiotics until osteomyelitis is ruled out,” Dr. Bridges said.

When a patient with one of these orthopedic conditions needs surgery, there are three considerations: preoperative transfusions to achieve hemoglobin level of 10 mg/dL for major procedures; no transfusions for arthroscopy and small closed reductions; and postoperative oxygenation and hydration to prevent a vaso-occlusive event and acute chest syndrome, he said.

Dr. Bridges reported having no conflicts of interest.

FORT LAUDERDALE, FLA. – Orthopedic crises are common in patients with sickle cell disease, ranging from osteonecrosis to bone infarction, and physicians who manage these patients should know how to recognize these crises and not hesitate to consult an orthopedic surgeon early on, according to one expert at the annual meeting of the Foundation for Sickle Cell Disease Research.

Richard Mark Kirkner/MDedge News

“Sickle cell is a common entity in orthopedic surgery, so you shouldn’t hesitate in the hospital or outpatient settings to call for an orthopedic surgeon when you’re dealing with acute pain crises, medullary infarcts, and osteonecrosis,” said Mark W. Bridges, MD, an orthopedic surgeon with Orthopaedic Associates in Southern Florida.

Dr. Bridges noted that the femoral head is the most common location for osteonecrosis, one of the four major orthopedic manifestations of sickle cell disease that he reviewed. The others are septic arthritis, osteomyelitis, and bone infarction.

“Bone infarction is more common than osteomyelitis, and gadolinium-enhanced MRI can help to differentiate the two,” he said.

Osteonecrosis occurs when ischemic cells die, weakening the subchondral bone. Besides the femoral head, osteonecrosis commonly affects the humeral head of the shoulder and the femoral condyles of the knee. Dr. Bridges reviewed the five stages of the Ficat and Arlet classification of osteonecrosis:

• 0 – no pain, normal x-rays.
• I – pain, normal x-rays but abnormal MRI.
• II – pain, abnormal x-ray (sclerosis without collapse).
• III – pain (subchondral collapse without joint degeneration).
• IV – pain (arthritic changes with subchondral collapse).

For osteonecrosis of the shoulder, Dr. Bridges said four surgical options exist: core decompression for stages I and II; humeral head resurfacing for stages II and III; and hemiarthroplasty or total shoulder replacement for stages III and IV.

“No medical therapies are known to slow the progression,” he said.

Total joint replacement can be inevitable in these patients when total collapse of the joint occurs, but Dr. Bridges added a word of caution. “Overall when it comes down to replacing joints, there are more complications in patients that have [sickle cell disease],” he said. “Normally the complication rate is about 1%; that typically goes up to about 10% in SCD patients, but when you have a patient with end-stage disease – shoulder collapse or hip collapse – you have to do something.”

Septic arthritis is an infection within the joint space, most commonly the hip, and it affects 5% of children and 0.3% of adults with sickle cell disease (Clin Orthop Relat Res. 2010;468:1676-81).

“This is very similar to a vaso-occlusive crisis,” Dr. Bridges said.

MRI with gadolinium can help guide treatment, and blood cultures and joint aspiration can identify the infectious microbe. Staphylococcus aureus is the most common, Dr. Bridges said. Treatment consists of IV antibiotics, irrigation, and debridement.

Osteomyelitis is an infection within the bone with symptoms similar to those of septic arthritis, although osteomyelitis patients are typically sicker, he said. MRI with gadolinium is indicated in patients who don’t respond to IV fluid, oxygenation, and nonsteroidal anti-inflammatory drugs. “Try to treat them like they have vaso-occlusive crisis,” he said. Blood cultures usually suffice in these patients; bone aspiration is rarely needed, Dr. Bridges said.

The most common organisms are Staphylococcus aureus and Salmonella, and sickle cell disease patients can have infections in more than one location, Dr. Bridges noted.

“If IV antibiotics don’t work, then these patients need surgical debridement,” he added.

Adults are prone to a higher rate of complications than are children, including joint stiffness, osteonecrosis, pathologic fracture, and chronic osteomyelitis.

Ischemic marrow from vaso-occlusion can result in bone infarction. With its severe pain, swelling, erythema, and loss of motion, bone infarction can appear similar to osteomyelitis and septic arthritis, although a high-grade fever is uncommon in bone infarction. Unlike osteomyelitis, gadolinium on MRI does not enhance in bone infarction.

Treatment “consists of supportive management with pain medications, hydration, and antibiotics until osteomyelitis is ruled out,” Dr. Bridges said.

When a patient with one of these orthopedic conditions needs surgery, there are three considerations: preoperative transfusions to achieve hemoglobin level of 10 mg/dL for major procedures; no transfusions for arthroscopy and small closed reductions; and postoperative oxygenation and hydration to prevent a vaso-occlusive event and acute chest syndrome, he said.

Dr. Bridges reported having no conflicts of interest.

FORT LAUDERDALE, FLA. – Orthopedic crises are common in patients with sickle cell disease, ranging from osteonecrosis to bone infarction, and physicians who manage these patients should know how to recognize these crises and not hesitate to consult an orthopedic surgeon early on, according to one expert at the annual meeting of the Foundation for Sickle Cell Disease Research.

Richard Mark Kirkner/MDedge News

“Sickle cell is a common entity in orthopedic surgery, so you shouldn’t hesitate in the hospital or outpatient settings to call for an orthopedic surgeon when you’re dealing with acute pain crises, medullary infarcts, and osteonecrosis,” said Mark W. Bridges, MD, an orthopedic surgeon with Orthopaedic Associates in Southern Florida.

Dr. Bridges noted that the femoral head is the most common location for osteonecrosis, one of the four major orthopedic manifestations of sickle cell disease that he reviewed. The others are septic arthritis, osteomyelitis, and bone infarction.

“Bone infarction is more common than osteomyelitis, and gadolinium-enhanced MRI can help to differentiate the two,” he said.

Osteonecrosis occurs when ischemic cells die, weakening the subchondral bone. Besides the femoral head, osteonecrosis commonly affects the humeral head of the shoulder and the femoral condyles of the knee. Dr. Bridges reviewed the five stages of the Ficat and Arlet classification of osteonecrosis:

• 0 – no pain, normal x-rays.
• I – pain, normal x-rays but abnormal MRI.
• II – pain, abnormal x-ray (sclerosis without collapse).
• III – pain (subchondral collapse without joint degeneration).
• IV – pain (arthritic changes with subchondral collapse).

For osteonecrosis of the shoulder, Dr. Bridges said four surgical options exist: core decompression for stages I and II; humeral head resurfacing for stages II and III; and hemiarthroplasty or total shoulder replacement for stages III and IV.

“No medical therapies are known to slow the progression,” he said.

Total joint replacement can be inevitable in these patients when total collapse of the joint occurs, but Dr. Bridges added a word of caution. “Overall when it comes down to replacing joints, there are more complications in patients that have [sickle cell disease],” he said. “Normally the complication rate is about 1%; that typically goes up to about 10% in SCD patients, but when you have a patient with end-stage disease – shoulder collapse or hip collapse – you have to do something.”

Septic arthritis is an infection within the joint space, most commonly the hip, and it affects 5% of children and 0.3% of adults with sickle cell disease (Clin Orthop Relat Res. 2010;468:1676-81).

“This is very similar to a vaso-occlusive crisis,” Dr. Bridges said.

MRI with gadolinium can help guide treatment, and blood cultures and joint aspiration can identify the infectious microbe. Staphylococcus aureus is the most common, Dr. Bridges said. Treatment consists of IV antibiotics, irrigation, and debridement.

Osteomyelitis is an infection within the bone with symptoms similar to those of septic arthritis, although osteomyelitis patients are typically sicker, he said. MRI with gadolinium is indicated in patients who don’t respond to IV fluid, oxygenation, and nonsteroidal anti-inflammatory drugs. “Try to treat them like they have vaso-occlusive crisis,” he said. Blood cultures usually suffice in these patients; bone aspiration is rarely needed, Dr. Bridges said.

The most common organisms are Staphylococcus aureus and Salmonella, and sickle cell disease patients can have infections in more than one location, Dr. Bridges noted.

“If IV antibiotics don’t work, then these patients need surgical debridement,” he added.

Adults are prone to a higher rate of complications than are children, including joint stiffness, osteonecrosis, pathologic fracture, and chronic osteomyelitis.

Ischemic marrow from vaso-occlusion can result in bone infarction. With its severe pain, swelling, erythema, and loss of motion, bone infarction can appear similar to osteomyelitis and septic arthritis, although a high-grade fever is uncommon in bone infarction. Unlike osteomyelitis, gadolinium on MRI does not enhance in bone infarction.

Treatment “consists of supportive management with pain medications, hydration, and antibiotics until osteomyelitis is ruled out,” Dr. Bridges said.

When a patient with one of these orthopedic conditions needs surgery, there are three considerations: preoperative transfusions to achieve hemoglobin level of 10 mg/dL for major procedures; no transfusions for arthroscopy and small closed reductions; and postoperative oxygenation and hydration to prevent a vaso-occlusive event and acute chest syndrome, he said.

Dr. Bridges reported having no conflicts of interest.