User login
Pegfilgrastim biosimilar approved by EC
The European Commission (EC) has granted marketing authorization for Sandoz’s pegfilgrastim product Ziextenzo®, a biosimilar of Amgen’s Neulasta.
Ziextenzo is approved for the same use as the reference medicine—to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies except chronic myeloid leukemia and myelodysplastic syndromes.
The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.
The EC’s approval was based on research suggesting Ziextenzo is comparable to Neulasta in terms of safety, efficacy, pharmacokinetics, and pharmacodynamics.1,2,3,4
1. Blackwell K. et al. Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol 28, 2272-2277 (2017).
2. Nakov R. et al. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects. 2017 San Antonio Breast Cancer Symposium, abstract P3-14-10.
3. Blackwell K. et al. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist 21, 789-794 (2016).
4. Harbeck N. et al. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol 12, 1359-1367 (2016).
The European Commission (EC) has granted marketing authorization for Sandoz’s pegfilgrastim product Ziextenzo®, a biosimilar of Amgen’s Neulasta.
Ziextenzo is approved for the same use as the reference medicine—to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies except chronic myeloid leukemia and myelodysplastic syndromes.
The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.
The EC’s approval was based on research suggesting Ziextenzo is comparable to Neulasta in terms of safety, efficacy, pharmacokinetics, and pharmacodynamics.1,2,3,4
1. Blackwell K. et al. Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol 28, 2272-2277 (2017).
2. Nakov R. et al. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects. 2017 San Antonio Breast Cancer Symposium, abstract P3-14-10.
3. Blackwell K. et al. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist 21, 789-794 (2016).
4. Harbeck N. et al. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol 12, 1359-1367 (2016).
The European Commission (EC) has granted marketing authorization for Sandoz’s pegfilgrastim product Ziextenzo®, a biosimilar of Amgen’s Neulasta.
Ziextenzo is approved for the same use as the reference medicine—to reduce the duration of neutropenia and the incidence of febrile neutropenia in adults receiving cytotoxic chemotherapy for malignancies except chronic myeloid leukemia and myelodysplastic syndromes.
The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.
The EC’s approval was based on research suggesting Ziextenzo is comparable to Neulasta in terms of safety, efficacy, pharmacokinetics, and pharmacodynamics.1,2,3,4
1. Blackwell K. et al. Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Ann Oncol 28, 2272-2277 (2017).
2. Nakov R. et al. Proposed biosimilar pegfilgrastim LA-EP2006 shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects. 2017 San Antonio Breast Cancer Symposium, abstract P3-14-10.
3. Blackwell K. et al. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial. Oncologist 21, 789-794 (2016).
4. Harbeck N. et al. Randomized, double-blind study comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer. Future Oncol 12, 1359-1367 (2016).
EC approves pegfilgrastim biosimilar
The European Commission (EC) has approved Mundipharma’s pegfilgrastim product Pelmeg, a biosimilar of Amgen’s Neulasta.
Pelmeg is approved for use in reducing the duration of neutropenia and the incidence of febrile neutropenia in adults who receive cytotoxic chemotherapy for malignancies, with the exceptions of chronic myeloid leukemia and myelodysplastic syndromes.
The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.
The EC’s approval of Pelmeg was supported by research showing pharmacokinetic comparability between Pelmeg and Neulasta at a dose of 6 mg, pharmacodynamic comparability at doses of 6 mg and 3 mg, and no clinically meaningful differences in the safety and immunogenicity profiles of Pelmeg and Neulasta.1,2,3
1. Roth K. et al. Demonstration of pharmacokinetic and pharmacodynamic comparability in healthy volunteers for B12019, a proposed pegfilgrastim biosimilar. ECCO 2017, abstract 241.
2. Roth K. et al. Comparability of pharmacodynamics and immunogenicity of B12019, a proposed pegfilgrastim biosimilar to Neulasta®. ASH 2017, abstract 1002.
3. Roth K. et al. Pharmacokinetic and pharmacodynamic comparability of B12019, a proposed pegfilgrastim biosimilar. ESMO 2017, poster 1573.
The European Commission (EC) has approved Mundipharma’s pegfilgrastim product Pelmeg, a biosimilar of Amgen’s Neulasta.
Pelmeg is approved for use in reducing the duration of neutropenia and the incidence of febrile neutropenia in adults who receive cytotoxic chemotherapy for malignancies, with the exceptions of chronic myeloid leukemia and myelodysplastic syndromes.
The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.
The EC’s approval of Pelmeg was supported by research showing pharmacokinetic comparability between Pelmeg and Neulasta at a dose of 6 mg, pharmacodynamic comparability at doses of 6 mg and 3 mg, and no clinically meaningful differences in the safety and immunogenicity profiles of Pelmeg and Neulasta.1,2,3
1. Roth K. et al. Demonstration of pharmacokinetic and pharmacodynamic comparability in healthy volunteers for B12019, a proposed pegfilgrastim biosimilar. ECCO 2017, abstract 241.
2. Roth K. et al. Comparability of pharmacodynamics and immunogenicity of B12019, a proposed pegfilgrastim biosimilar to Neulasta®. ASH 2017, abstract 1002.
3. Roth K. et al. Pharmacokinetic and pharmacodynamic comparability of B12019, a proposed pegfilgrastim biosimilar. ESMO 2017, poster 1573.
The European Commission (EC) has approved Mundipharma’s pegfilgrastim product Pelmeg, a biosimilar of Amgen’s Neulasta.
Pelmeg is approved for use in reducing the duration of neutropenia and the incidence of febrile neutropenia in adults who receive cytotoxic chemotherapy for malignancies, with the exceptions of chronic myeloid leukemia and myelodysplastic syndromes.
The approval is valid in all countries of the European Union as well as Norway, Iceland, and Liechtenstein.
The EC’s approval of Pelmeg was supported by research showing pharmacokinetic comparability between Pelmeg and Neulasta at a dose of 6 mg, pharmacodynamic comparability at doses of 6 mg and 3 mg, and no clinically meaningful differences in the safety and immunogenicity profiles of Pelmeg and Neulasta.1,2,3
1. Roth K. et al. Demonstration of pharmacokinetic and pharmacodynamic comparability in healthy volunteers for B12019, a proposed pegfilgrastim biosimilar. ECCO 2017, abstract 241.
2. Roth K. et al. Comparability of pharmacodynamics and immunogenicity of B12019, a proposed pegfilgrastim biosimilar to Neulasta®. ASH 2017, abstract 1002.
3. Roth K. et al. Pharmacokinetic and pharmacodynamic comparability of B12019, a proposed pegfilgrastim biosimilar. ESMO 2017, poster 1573.
Ins and outs of SCD treatment to be covered at ASH
Sickle cell disease (SCD) will take center stage at the 2018 ASH Annual Meeting, according to a recent press briefing.
During the briefing, ASH President Alexis A. Thompson, MD, highlighted four “abstracts to watch” that focus on SCD.
These abstracts cover a pilot study of gene therapy, long-term outcomes of haploidentical hematopoietic stem cell transplant (haplo-HSCT), mortality rates in SCD patients prescribed opioids, and outcomes with hydroxyurea (HU) among patients in sub-Saharan Africa.
“These are all quite different aspects of work being done,” said Dr. Thompson, of Ann and Robert H. Lurie Children’s Hospital of Chicago in Illinois.
Gene therapy
In the pilot study of gene therapy (abstract 1023), investigators used a microRNA-adapted short hairpin RNA lentiviral vector targeting BCL11A for autologous gene therapy in SCD patients.
Preclinical research had shown that this approach could induce fetal hemoglobin in human erythroid cells and “largely” attenuate the hematologic effects of SCD in a murine model, according to investigators.
Initial results from the pilot study suggest this approach is feasible in humans as well. In the first patient infused, investigators observed “rapid” induction of fetal hemoglobin and “marked attenuation of hemolysis in the early phase of autologous reconstitution.”
“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said.
Haplo-HSCT
In another study (abstract 162), investigators assessed long-term health-related quality of life in high-risk SCD patients who underwent familial haplo-HSCT.
The patients received myeloablative conditioning and familial haplo-HSCT using CD34 enrichment and mononuclear cell (CD3) addback.
Two years from haplo-HSCT, patients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.
Opioid use
A third study (abstract 315) indicates that opioid use is not associated with in-hospital mortality in SCD patients.
This is interesting in the context of the national opioid epidemic, Dr. Thompson said.
Investigators looked at data from the National Inpatient Sample and found no significant increase in in-hospital mortality in SCD patients from 1998 through 2013. This can be compared to the 350% increase in non-SCD opioid prescription-related deaths from 1999 through 2013.
“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”
HU in sub-Saharan Africa
Dr. Thompson said a fourth study worth watching is REACH (abstract 3), a trial of HU in 635 children in sub-Saharan Africa.
The study provides the first prospective data showing the feasibility, safety, and benefits of HU use in this population, according to investigators.
The findings are “quite encouraging,” Dr. Thompson said.
She added that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.
Sickle cell disease (SCD) will take center stage at the 2018 ASH Annual Meeting, according to a recent press briefing.
During the briefing, ASH President Alexis A. Thompson, MD, highlighted four “abstracts to watch” that focus on SCD.
These abstracts cover a pilot study of gene therapy, long-term outcomes of haploidentical hematopoietic stem cell transplant (haplo-HSCT), mortality rates in SCD patients prescribed opioids, and outcomes with hydroxyurea (HU) among patients in sub-Saharan Africa.
“These are all quite different aspects of work being done,” said Dr. Thompson, of Ann and Robert H. Lurie Children’s Hospital of Chicago in Illinois.
Gene therapy
In the pilot study of gene therapy (abstract 1023), investigators used a microRNA-adapted short hairpin RNA lentiviral vector targeting BCL11A for autologous gene therapy in SCD patients.
Preclinical research had shown that this approach could induce fetal hemoglobin in human erythroid cells and “largely” attenuate the hematologic effects of SCD in a murine model, according to investigators.
Initial results from the pilot study suggest this approach is feasible in humans as well. In the first patient infused, investigators observed “rapid” induction of fetal hemoglobin and “marked attenuation of hemolysis in the early phase of autologous reconstitution.”
“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said.
Haplo-HSCT
In another study (abstract 162), investigators assessed long-term health-related quality of life in high-risk SCD patients who underwent familial haplo-HSCT.
The patients received myeloablative conditioning and familial haplo-HSCT using CD34 enrichment and mononuclear cell (CD3) addback.
Two years from haplo-HSCT, patients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.
Opioid use
A third study (abstract 315) indicates that opioid use is not associated with in-hospital mortality in SCD patients.
This is interesting in the context of the national opioid epidemic, Dr. Thompson said.
Investigators looked at data from the National Inpatient Sample and found no significant increase in in-hospital mortality in SCD patients from 1998 through 2013. This can be compared to the 350% increase in non-SCD opioid prescription-related deaths from 1999 through 2013.
“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”
HU in sub-Saharan Africa
Dr. Thompson said a fourth study worth watching is REACH (abstract 3), a trial of HU in 635 children in sub-Saharan Africa.
The study provides the first prospective data showing the feasibility, safety, and benefits of HU use in this population, according to investigators.
The findings are “quite encouraging,” Dr. Thompson said.
She added that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.
Sickle cell disease (SCD) will take center stage at the 2018 ASH Annual Meeting, according to a recent press briefing.
During the briefing, ASH President Alexis A. Thompson, MD, highlighted four “abstracts to watch” that focus on SCD.
These abstracts cover a pilot study of gene therapy, long-term outcomes of haploidentical hematopoietic stem cell transplant (haplo-HSCT), mortality rates in SCD patients prescribed opioids, and outcomes with hydroxyurea (HU) among patients in sub-Saharan Africa.
“These are all quite different aspects of work being done,” said Dr. Thompson, of Ann and Robert H. Lurie Children’s Hospital of Chicago in Illinois.
Gene therapy
In the pilot study of gene therapy (abstract 1023), investigators used a microRNA-adapted short hairpin RNA lentiviral vector targeting BCL11A for autologous gene therapy in SCD patients.
Preclinical research had shown that this approach could induce fetal hemoglobin in human erythroid cells and “largely” attenuate the hematologic effects of SCD in a murine model, according to investigators.
Initial results from the pilot study suggest this approach is feasible in humans as well. In the first patient infused, investigators observed “rapid” induction of fetal hemoglobin and “marked attenuation of hemolysis in the early phase of autologous reconstitution.”
“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said.
Haplo-HSCT
In another study (abstract 162), investigators assessed long-term health-related quality of life in high-risk SCD patients who underwent familial haplo-HSCT.
The patients received myeloablative conditioning and familial haplo-HSCT using CD34 enrichment and mononuclear cell (CD3) addback.
Two years from haplo-HSCT, patients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.
Opioid use
A third study (abstract 315) indicates that opioid use is not associated with in-hospital mortality in SCD patients.
This is interesting in the context of the national opioid epidemic, Dr. Thompson said.
Investigators looked at data from the National Inpatient Sample and found no significant increase in in-hospital mortality in SCD patients from 1998 through 2013. This can be compared to the 350% increase in non-SCD opioid prescription-related deaths from 1999 through 2013.
“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”
HU in sub-Saharan Africa
Dr. Thompson said a fourth study worth watching is REACH (abstract 3), a trial of HU in 635 children in sub-Saharan Africa.
The study provides the first prospective data showing the feasibility, safety, and benefits of HU use in this population, according to investigators.
The findings are “quite encouraging,” Dr. Thompson said.
She added that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.
ASH 2018 coming attractions look at the big picture
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
In the closest thing the medical world has to movie trailers, the American Society of Hematology held a press conference offering
Shorter R-CHOP regimen for DLBCL
Under the heading “Big Trials, Big Results” will be data from the FLYER trial, a phase 3, randomized, deescalation trial in 592 patients aged 18-60 years with favorable-prognosis diffuse large B-cell lymphoma. The investigators report that both progression-free survival and overall survival with four cycles of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone) were noninferior to those for patients treated with six cycles of R-CHOP (abstract 781).
Ibrutinib mastery in CLL
Also on the program are results of a study showing that ibrutinib (Imbruvica), either alone or in combination with rituximab, is associated with superior progression-free survival than bendamustine and rituximab in older patients with chronic lymphocytic leukemia (CLL).
The trial, the Alliance North American Intergroup Study A041202 (abstract 6) is the first major trial to pit ibrutinib against the modern standard of immunochemotherapy rather than the older standard of chlorambucil, Dr. Brodsky noted.
Anemia support in beta-thalassemia, MDS
In nonmalignant disease, investigators in the randomized, phase 3 BELIEVE trial are reporting results of their study showing that the first-in-class erythroid maturation agent luspatercept was associated with significant reductions in the need for RBC transfusion in adults with transfusion-dependent beta-thalassemia.
The investigators report that the experimental agent was “generally well tolerated” (abstract 163).
“Beyond a proof of principle, [this is] certainly a very exciting advancement in this group of patients who otherwise had very few treatment options,” said Alexis A. Thompson, MD, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, and the current ASH president.
Dr. Thompson also highlighted the MEDALIST trial (abstract 1), a phase 3, randomized study showing that luspatercept significantly reduced transfusion burden, compared with placebo, in patients with anemia caused by very low–, low-, or intermediate-risk myelodysplastic syndrome with ring sideroblasts who require RBC transfusions.
“This group of patients were individuals who were refractory or were not responders or did not tolerate erythropoietic stimulating agents and therefore were requiring regular transfusion,” Dr. Thompson said.
Worth the wait
The late-breaking abstract program was stretched from the usual six abstracts to seven this year because of the unusually high quality of the science, Dr. Brodsky said.
Among these star attractions are results of a phase 3, randomized study of daratumumab (Darzalex) plus lenalidomide and dexamethasone versus lenalidomide-dexamethasone alone for patients with newly diagnosed multiple myeloma who are ineligible for transplant.
The investigators found that adding daratumumab reduced the risk of disease progression or death by close to 50%, supporting the combination as a new standard of care in these patients, according to Thierry Facon, MD, from the Hospital Claude Huriez in Lille, France, and colleagues (abstract LBA-2).
Two other late-breakers deal with CLL. The first, a randomized, phase 3 study of ibrutinib-based therapy versus standard fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy in younger patients with untreated CLL, found that ibrutinib and rituximab provided significantly better progression-free survival and overall survival (abstract LBA-4).
“These findings have immediate practice-changing implications and establish ibrutinib-based therapy as the most efficacious first-line therapy for patients with CLL,” wrote Tait D. Shanafelt, MD, from Stanford (Calif.) University, and colleagues.
On a less positive note, Australian researchers report their discovery of a recurrent mutation in BCL2 that confers resistance to venetoclax (Venclexta) in patients with progressive CLL (abstract LBA-7).
“This mutation provides new insights into the pathobiology of venetoclax resistance and provides a potential biomarker of impending clinical relapse,” wrote Piers Blombery, MBBS, from the University of Melbourne, and colleagues.
Finally, investigators from children’s hospitals in the United States and Europe report promising findings on the safety and efficacy of emapalumab for the treatment of patients with the rare genetic disorder primary hemophagocytic lymphohistiocytosis (HLH).
The drug, newly approved by the Food and Drug Administration, was able to control HLH’s hyperinflammatory activity, and allowed a substantial proportion of patients to survive to hematopoietic stem cell transplantation, the investigators said (abstract LBA-6).
Sickle cell disease: What to watch at ASH
Sickle cell disease will take center stage at the annual meeting of the American Society of Hematology.
, long-term outcomes of haploidentical transplants, mortality rates in patients prescribed opioids, and aspects of care in lower-resource countries, according to Alexis A. Thompson, MD, the current ASH president.
“These are all quite different aspects of work being done,” said Dr. Thompson, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
In the gene therapy study (abstract 1023), investigators will report initial results of genetic targeting of the fetal-to-adult globin switch in sickle cell patients. The clinical pilot study involves autologous gene therapy utilizing microRNA-adapted shRNAs (shRNAmiR) lentiviral vector targeting BCL11A, a repressor of gamma globin expression, according to the investigators.
“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said in a media briefing.
In another study (abstract 162), investigators will report long-term results of familial haploidentical stem cell transplantation (HISCT) showing that high-risk sickle cell patients had significantly improved health-related quality of life in long-term follow-up.
Two years after myeloablative conditioning and familial HISCT using CD34 enrichment and mononuclear cell (CD3) addback, recipients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.
Another study, which is interesting in the context of the national opioid epidemic, Dr. Thompson said, will show that opioid use was not associated with in-hospital mortality in patients with sickle cell disease (abstract 315).
Looking at data from the National Inpatient Sample, there was no increase in in-hospital mortality in sickle cell patients versus the general population since the onset of the epidemic, which has been documented since 2000, according to the investigators.
“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”
One final study worth watching, according to Dr. Thompson, is REACH, a prospective, multinational trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa (abstract 3).
The study, which included 635 children, provides the first prospective data showing the feasibility, safety, and benefits of hydroxyurea treatment for children with sickle cell anemia in sub-Saharan Africa, according to the investigators.
The findings are “quite encouraging,” said Dr. Thompson, adding that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.
Sickle cell disease will take center stage at the annual meeting of the American Society of Hematology.
, long-term outcomes of haploidentical transplants, mortality rates in patients prescribed opioids, and aspects of care in lower-resource countries, according to Alexis A. Thompson, MD, the current ASH president.
“These are all quite different aspects of work being done,” said Dr. Thompson, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
In the gene therapy study (abstract 1023), investigators will report initial results of genetic targeting of the fetal-to-adult globin switch in sickle cell patients. The clinical pilot study involves autologous gene therapy utilizing microRNA-adapted shRNAs (shRNAmiR) lentiviral vector targeting BCL11A, a repressor of gamma globin expression, according to the investigators.
“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said in a media briefing.
In another study (abstract 162), investigators will report long-term results of familial haploidentical stem cell transplantation (HISCT) showing that high-risk sickle cell patients had significantly improved health-related quality of life in long-term follow-up.
Two years after myeloablative conditioning and familial HISCT using CD34 enrichment and mononuclear cell (CD3) addback, recipients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.
Another study, which is interesting in the context of the national opioid epidemic, Dr. Thompson said, will show that opioid use was not associated with in-hospital mortality in patients with sickle cell disease (abstract 315).
Looking at data from the National Inpatient Sample, there was no increase in in-hospital mortality in sickle cell patients versus the general population since the onset of the epidemic, which has been documented since 2000, according to the investigators.
“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”
One final study worth watching, according to Dr. Thompson, is REACH, a prospective, multinational trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa (abstract 3).
The study, which included 635 children, provides the first prospective data showing the feasibility, safety, and benefits of hydroxyurea treatment for children with sickle cell anemia in sub-Saharan Africa, according to the investigators.
The findings are “quite encouraging,” said Dr. Thompson, adding that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.
Sickle cell disease will take center stage at the annual meeting of the American Society of Hematology.
, long-term outcomes of haploidentical transplants, mortality rates in patients prescribed opioids, and aspects of care in lower-resource countries, according to Alexis A. Thompson, MD, the current ASH president.
“These are all quite different aspects of work being done,” said Dr. Thompson, associate director of equity and minority health at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.
In the gene therapy study (abstract 1023), investigators will report initial results of genetic targeting of the fetal-to-adult globin switch in sickle cell patients. The clinical pilot study involves autologous gene therapy utilizing microRNA-adapted shRNAs (shRNAmiR) lentiviral vector targeting BCL11A, a repressor of gamma globin expression, according to the investigators.
“We’re looking forward to seeing this initial presentation on their findings with this first administration to humans,” Dr. Thompson said in a media briefing.
In another study (abstract 162), investigators will report long-term results of familial haploidentical stem cell transplantation (HISCT) showing that high-risk sickle cell patients had significantly improved health-related quality of life in long-term follow-up.
Two years after myeloablative conditioning and familial HISCT using CD34 enrichment and mononuclear cell (CD3) addback, recipients had significant improvements in emotional and physical health-related quality of life, among other outcomes of interest, including neurocognitive outcomes.
Another study, which is interesting in the context of the national opioid epidemic, Dr. Thompson said, will show that opioid use was not associated with in-hospital mortality in patients with sickle cell disease (abstract 315).
Looking at data from the National Inpatient Sample, there was no increase in in-hospital mortality in sickle cell patients versus the general population since the onset of the epidemic, which has been documented since 2000, according to the investigators.
“It should alleviate many concerns about patients with sickle cell who, for legitimate reasons, may require high doses of opioids,” Dr. Thompson said. “While I think we’re being very mindful about opioid use in this patient population, they certainly do need these high doses, but there does not seem to be an extraordinary risk of death associated with their use.”
One final study worth watching, according to Dr. Thompson, is REACH, a prospective, multinational trial of hydroxyurea for sickle cell anemia in sub-Saharan Africa (abstract 3).
The study, which included 635 children, provides the first prospective data showing the feasibility, safety, and benefits of hydroxyurea treatment for children with sickle cell anemia in sub-Saharan Africa, according to the investigators.
The findings are “quite encouraging,” said Dr. Thompson, adding that the results looked “very similar” to the United States experience and demonstrated effective clinical trial design and execution in a lower-resource country.
FDA approves first treatment for primary HLH
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
Adjunctive Promacta approved for first-line SAA
The Food and Drug Administration has approved use of eltrombopag (Promacta) for patients severe aplastic anemia (SAA), Novartis announced Nov. 16.
The agency’s move means that eltrombopag, a synthetic thrombopoietin-receptor agonist, is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults, and pediatric patients aged 2 and older with SAA. The drug received breakthrough therapy designation and priority review for this indication, the company said in a press release.
In addition, eltrombopag is FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, those with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and those with thrombocytopenia and with chronic hepatitis C infection.
. The trial included 153 previously untreated SAA patients aged 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag in the trial was 150 mg once daily for patients aged 12 and older (75 mg for East and Southeast Asians), 75 mg once daily for patients aged 6 to 11 (37.5 mg for East and Southeast Asians), and 2.5 mg/kg once daily for patients aged 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules. The recommended schedule from the third cohort (n = 92) was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%. The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were increases in ALT (29%), AST (17%), and blood bilirubin (17%). Also, rash (8%), and skin discoloration, including hyperpigmentation (5%), were cited as adverse events.
Updated results from the trial are available in the prescribing information for eltrombopag. In most countries outside of the United States, the drug is marketed as Revolade.
The Food and Drug Administration has approved use of eltrombopag (Promacta) for patients severe aplastic anemia (SAA), Novartis announced Nov. 16.
The agency’s move means that eltrombopag, a synthetic thrombopoietin-receptor agonist, is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults, and pediatric patients aged 2 and older with SAA. The drug received breakthrough therapy designation and priority review for this indication, the company said in a press release.
In addition, eltrombopag is FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, those with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and those with thrombocytopenia and with chronic hepatitis C infection.
. The trial included 153 previously untreated SAA patients aged 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag in the trial was 150 mg once daily for patients aged 12 and older (75 mg for East and Southeast Asians), 75 mg once daily for patients aged 6 to 11 (37.5 mg for East and Southeast Asians), and 2.5 mg/kg once daily for patients aged 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules. The recommended schedule from the third cohort (n = 92) was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%. The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were increases in ALT (29%), AST (17%), and blood bilirubin (17%). Also, rash (8%), and skin discoloration, including hyperpigmentation (5%), were cited as adverse events.
Updated results from the trial are available in the prescribing information for eltrombopag. In most countries outside of the United States, the drug is marketed as Revolade.
The Food and Drug Administration has approved use of eltrombopag (Promacta) for patients severe aplastic anemia (SAA), Novartis announced Nov. 16.
The agency’s move means that eltrombopag, a synthetic thrombopoietin-receptor agonist, is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults, and pediatric patients aged 2 and older with SAA. The drug received breakthrough therapy designation and priority review for this indication, the company said in a press release.
In addition, eltrombopag is FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, those with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and those with thrombocytopenia and with chronic hepatitis C infection.
. The trial included 153 previously untreated SAA patients aged 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag in the trial was 150 mg once daily for patients aged 12 and older (75 mg for East and Southeast Asians), 75 mg once daily for patients aged 6 to 11 (37.5 mg for East and Southeast Asians), and 2.5 mg/kg once daily for patients aged 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules. The recommended schedule from the third cohort (n = 92) was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%. The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were increases in ALT (29%), AST (17%), and blood bilirubin (17%). Also, rash (8%), and skin discoloration, including hyperpigmentation (5%), were cited as adverse events.
Updated results from the trial are available in the prescribing information for eltrombopag. In most countries outside of the United States, the drug is marketed as Revolade.
Eltrombopag approved as first-line SAA therapy
The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).
Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.
Eltrombopag received breakthrough therapy designation and priority review for this indication.
Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.
The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.
Updated results from the trial are available in the prescribing information for eltrombopag.
The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag was:
- 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
- 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
- 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules.
The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.
The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).
Eltrombopag is a product of Novartis.
The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).
Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.
Eltrombopag received breakthrough therapy designation and priority review for this indication.
Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.
The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.
Updated results from the trial are available in the prescribing information for eltrombopag.
The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag was:
- 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
- 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
- 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules.
The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.
The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).
Eltrombopag is a product of Novartis.
The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).
Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.
Eltrombopag received breakthrough therapy designation and priority review for this indication.
Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.
The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.
Updated results from the trial are available in the prescribing information for eltrombopag.
The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.
The starting dose of eltrombopag was:
- 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
- 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
- 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).
Patients were divided into three cohorts with different dosing schedules.
The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.
Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.
The median duration of both overall and complete response was 24.3 months.
The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).
Eltrombopag is a product of Novartis.
FDA approves generic decitabine for MDS
The U.S. Food and Drug Administration has approved Lupin’s decitabine product, a generic version of Otsuka Pharmaceutical Co. Ltd.’s Dacogen, to treat patients with myelodysplastic syndromes (MDS).
Lupin’s decitabine for injection (50 mg, single-dose vial) is approved to treat patients with intermediate-1, intermediate-2, and high-risk MDS.
This includes previously treated, untreated, de novo, and secondary MDS of all French-American-British subtypes—refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
The U.S. Food and Drug Administration has approved Lupin’s decitabine product, a generic version of Otsuka Pharmaceutical Co. Ltd.’s Dacogen, to treat patients with myelodysplastic syndromes (MDS).
Lupin’s decitabine for injection (50 mg, single-dose vial) is approved to treat patients with intermediate-1, intermediate-2, and high-risk MDS.
This includes previously treated, untreated, de novo, and secondary MDS of all French-American-British subtypes—refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
The U.S. Food and Drug Administration has approved Lupin’s decitabine product, a generic version of Otsuka Pharmaceutical Co. Ltd.’s Dacogen, to treat patients with myelodysplastic syndromes (MDS).
Lupin’s decitabine for injection (50 mg, single-dose vial) is approved to treat patients with intermediate-1, intermediate-2, and high-risk MDS.
This includes previously treated, untreated, de novo, and secondary MDS of all French-American-British subtypes—refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia.
Score can predict thrombosis in ITP
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.