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Sickle cell disease phenotype reversed by gene therapy
SAN DIEGO – An adult with sickle cell disease has had significant remissions in symptoms and a near elimination of transfusion requirements after receiving an infusion of autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.
In a first-in-human, proof-of-concept study, transduction of hematopoietic stem cells with a lentiviral vector targeted against the gamma globin repressor BCL11A in erythroid cells led to rapid induction of fetal hemoglobin and a reversal of the sickle cell disease (SCD) phenotype in the early phase of stem cell reconstitution, reported Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston.
“The potential advantage of this approach over the gene-addition strategy of gene therapy is that we can harness the physiologic switch machinery that exists in the cell to simultaneously increase fetal hemoglobin and decrease sickle hemoglobin,” she said at a briefing prior to her presentation at the annual meeting of the American Society of Hematology.
Several research groups are developing autologous gene therapy for beta-hemoglobinopathies, including the use of CRISPR-Cas9 technology to mimic a rare, naturally occurring mutation that causes the fetal type of hemoglobin to persist into adulthood in some patients with SCD and beta-thalassemia.
Dr. Esrick and her colleagues are trying a different approach: Using gene therapy to knock down BCL11A expression to induce gamma globin expression.
For the treatment, autologous hematopoietic stem cells are collected from patients following mobilization with plerixafor. The cells are then transduced with a lentiviral vector consisting of a novel short hairpin RNA embedded in an endogenous micro-RNA. The investigators refer to the construct as a shmiR (“schmeer”). The construct is designed to be erythroid specific, with BCL11A knocked down only in the red cell lineage, to avoid potential off-target effects of the therapy.
Following stem cell collection and transduction, patients undergo conditioning with busulfan prior to infusion of the modified stem cells.
In three patients treated thus far, the process has been shown to be highly efficient, with approximately 96% of treated cells transduced.
In the patient mentioned before, neutrophil engraftment was confirmed on day 22 after transfusion of the modified cells. He experienced adverse events that were consistent with myeloablative conditioning, but no adverse events associated with the modified cells.
During 6 months of follow-up the patient did not experience SCD-related pain, respiratory events, or neurologic events, and did not have anemia, with a total hemoglobin of 11 g/dL at 6 months. He has not required any transfusions since engraftment.
Patients in the trial will be followed for 2 years, and then will be enrolled in a 15-year follow-up study designed to evaluate the safety and the durability of therapy.
Dr. Esrick reported receiving honoraria from Bluebird Bio, maker of the short hairpin RNA construct used in the trial.
SOURCE: Esrick EB et al. ASH 2018, Abstract 1023.
SAN DIEGO – An adult with sickle cell disease has had significant remissions in symptoms and a near elimination of transfusion requirements after receiving an infusion of autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.
In a first-in-human, proof-of-concept study, transduction of hematopoietic stem cells with a lentiviral vector targeted against the gamma globin repressor BCL11A in erythroid cells led to rapid induction of fetal hemoglobin and a reversal of the sickle cell disease (SCD) phenotype in the early phase of stem cell reconstitution, reported Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston.
“The potential advantage of this approach over the gene-addition strategy of gene therapy is that we can harness the physiologic switch machinery that exists in the cell to simultaneously increase fetal hemoglobin and decrease sickle hemoglobin,” she said at a briefing prior to her presentation at the annual meeting of the American Society of Hematology.
Several research groups are developing autologous gene therapy for beta-hemoglobinopathies, including the use of CRISPR-Cas9 technology to mimic a rare, naturally occurring mutation that causes the fetal type of hemoglobin to persist into adulthood in some patients with SCD and beta-thalassemia.
Dr. Esrick and her colleagues are trying a different approach: Using gene therapy to knock down BCL11A expression to induce gamma globin expression.
For the treatment, autologous hematopoietic stem cells are collected from patients following mobilization with plerixafor. The cells are then transduced with a lentiviral vector consisting of a novel short hairpin RNA embedded in an endogenous micro-RNA. The investigators refer to the construct as a shmiR (“schmeer”). The construct is designed to be erythroid specific, with BCL11A knocked down only in the red cell lineage, to avoid potential off-target effects of the therapy.
Following stem cell collection and transduction, patients undergo conditioning with busulfan prior to infusion of the modified stem cells.
In three patients treated thus far, the process has been shown to be highly efficient, with approximately 96% of treated cells transduced.
In the patient mentioned before, neutrophil engraftment was confirmed on day 22 after transfusion of the modified cells. He experienced adverse events that were consistent with myeloablative conditioning, but no adverse events associated with the modified cells.
During 6 months of follow-up the patient did not experience SCD-related pain, respiratory events, or neurologic events, and did not have anemia, with a total hemoglobin of 11 g/dL at 6 months. He has not required any transfusions since engraftment.
Patients in the trial will be followed for 2 years, and then will be enrolled in a 15-year follow-up study designed to evaluate the safety and the durability of therapy.
Dr. Esrick reported receiving honoraria from Bluebird Bio, maker of the short hairpin RNA construct used in the trial.
SOURCE: Esrick EB et al. ASH 2018, Abstract 1023.
SAN DIEGO – An adult with sickle cell disease has had significant remissions in symptoms and a near elimination of transfusion requirements after receiving an infusion of autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.
In a first-in-human, proof-of-concept study, transduction of hematopoietic stem cells with a lentiviral vector targeted against the gamma globin repressor BCL11A in erythroid cells led to rapid induction of fetal hemoglobin and a reversal of the sickle cell disease (SCD) phenotype in the early phase of stem cell reconstitution, reported Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston.
“The potential advantage of this approach over the gene-addition strategy of gene therapy is that we can harness the physiologic switch machinery that exists in the cell to simultaneously increase fetal hemoglobin and decrease sickle hemoglobin,” she said at a briefing prior to her presentation at the annual meeting of the American Society of Hematology.
Several research groups are developing autologous gene therapy for beta-hemoglobinopathies, including the use of CRISPR-Cas9 technology to mimic a rare, naturally occurring mutation that causes the fetal type of hemoglobin to persist into adulthood in some patients with SCD and beta-thalassemia.
Dr. Esrick and her colleagues are trying a different approach: Using gene therapy to knock down BCL11A expression to induce gamma globin expression.
For the treatment, autologous hematopoietic stem cells are collected from patients following mobilization with plerixafor. The cells are then transduced with a lentiviral vector consisting of a novel short hairpin RNA embedded in an endogenous micro-RNA. The investigators refer to the construct as a shmiR (“schmeer”). The construct is designed to be erythroid specific, with BCL11A knocked down only in the red cell lineage, to avoid potential off-target effects of the therapy.
Following stem cell collection and transduction, patients undergo conditioning with busulfan prior to infusion of the modified stem cells.
In three patients treated thus far, the process has been shown to be highly efficient, with approximately 96% of treated cells transduced.
In the patient mentioned before, neutrophil engraftment was confirmed on day 22 after transfusion of the modified cells. He experienced adverse events that were consistent with myeloablative conditioning, but no adverse events associated with the modified cells.
During 6 months of follow-up the patient did not experience SCD-related pain, respiratory events, or neurologic events, and did not have anemia, with a total hemoglobin of 11 g/dL at 6 months. He has not required any transfusions since engraftment.
Patients in the trial will be followed for 2 years, and then will be enrolled in a 15-year follow-up study designed to evaluate the safety and the durability of therapy.
Dr. Esrick reported receiving honoraria from Bluebird Bio, maker of the short hairpin RNA construct used in the trial.
SOURCE: Esrick EB et al. ASH 2018, Abstract 1023.
REPORTING FROM ASH 2018
Key clinical point: Gene therapy to induce the fetal form of hemoglobin reversed the symptoms of sickle cell disease in an adult patient.
Major finding: During 6 months of follow-up the patient did not experience sickle cell disease–related pain, respiratory events, or neurologic events, and did not have anemia.
Study details: A first-in-human study in seven adults with sickle cell disease.
Disclosures: Dr. Esrick reported receiving honoraria from Bluebird Bio, maker of the short hairpin RNA construct used in the trial.
Source: Esrick EB et al. ASH 2018, Abstract 1023.
Daily hydroxyurea effective, safe for African children
SAN DIEGO – Daily hydroxyurea treatment for sickle cell disease is feasible, safe, and effective for children in sub-Saharan Africa, according to the results of a large open-label, phase 1-2, international trial.
Hydroxyurea was associated with reduced rates of malaria and other infections, resulting in improved survival, according to Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, the Democratic Republic of the Congo.
“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” Dr. Tshilolo said in a press conference at the annual meeting of the American Society of Hematology.
Use of hydroxyurea has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to the researchers.
Moreover, most of the data on the efficacy of hydroxyurea come from studies conducted in the United States, Europe, and other high-income settings, said the study’s senior author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center.
“Now that there’s data in an African setting, I think this will go a long way to advancing [hydroxyurea therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said in an interview.
In the study by Dr. Ware, Dr. Tshilolo, and their colleagues, 606 children in four sub-Saharan African countries completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data. The children, who were aged 1-10 years, were started at 15-20 mg/kg of hydroxyurea for 6 months, followed by escalation to the maximum tolerated dose.
With a median of 2.5 years of treatment, treated children experienced less pain and anemia, fewer cases of malaria and other infections, and lower rates of transfusions and death versus rates observed in the pretreatment screening phase of the trial.
The rate of vasoocclusive pain during hydroxyurea treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio, 0.45; 95% confidence interval, 0.37-0.56), according to data simultaneously published in the New England Journal of Medicine.
Malaria infection rates were 22.9 events per 100 patient-years in the hydroxyurea treatment period versus 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66). Rates of nonmalaria infections were 90.0 events per 100 patient-years in the hydroxyurea treatment period versus 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).
Dr. Tshilolo said investigators were “encouraged” by the reduced infection rates, particularly in light of previous concerns that hydroxyurea could suppress the immune system and put children at risk for malaria.
Death rates were 1.1 per 100 patient-years in the hydroxyurea group and 3.6 per 100 patient-years in the pretreatment period (IR, 0.30; 95% CI, 0.10-0.88). Dose-limiting toxic events occurred in 5.1% of the children, which was below the protocol-specified threshold for safety, Dr. Tshilolo added.
Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the NIH/NHLBI and Bristol-Myers Squibb.
SOURCE: Tshilolo L et al. ASH 2018, Abstract 3.
SAN DIEGO – Daily hydroxyurea treatment for sickle cell disease is feasible, safe, and effective for children in sub-Saharan Africa, according to the results of a large open-label, phase 1-2, international trial.
Hydroxyurea was associated with reduced rates of malaria and other infections, resulting in improved survival, according to Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, the Democratic Republic of the Congo.
“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” Dr. Tshilolo said in a press conference at the annual meeting of the American Society of Hematology.
Use of hydroxyurea has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to the researchers.
Moreover, most of the data on the efficacy of hydroxyurea come from studies conducted in the United States, Europe, and other high-income settings, said the study’s senior author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center.
“Now that there’s data in an African setting, I think this will go a long way to advancing [hydroxyurea therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said in an interview.
In the study by Dr. Ware, Dr. Tshilolo, and their colleagues, 606 children in four sub-Saharan African countries completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data. The children, who were aged 1-10 years, were started at 15-20 mg/kg of hydroxyurea for 6 months, followed by escalation to the maximum tolerated dose.
With a median of 2.5 years of treatment, treated children experienced less pain and anemia, fewer cases of malaria and other infections, and lower rates of transfusions and death versus rates observed in the pretreatment screening phase of the trial.
The rate of vasoocclusive pain during hydroxyurea treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio, 0.45; 95% confidence interval, 0.37-0.56), according to data simultaneously published in the New England Journal of Medicine.
Malaria infection rates were 22.9 events per 100 patient-years in the hydroxyurea treatment period versus 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66). Rates of nonmalaria infections were 90.0 events per 100 patient-years in the hydroxyurea treatment period versus 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).
Dr. Tshilolo said investigators were “encouraged” by the reduced infection rates, particularly in light of previous concerns that hydroxyurea could suppress the immune system and put children at risk for malaria.
Death rates were 1.1 per 100 patient-years in the hydroxyurea group and 3.6 per 100 patient-years in the pretreatment period (IR, 0.30; 95% CI, 0.10-0.88). Dose-limiting toxic events occurred in 5.1% of the children, which was below the protocol-specified threshold for safety, Dr. Tshilolo added.
Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the NIH/NHLBI and Bristol-Myers Squibb.
SOURCE: Tshilolo L et al. ASH 2018, Abstract 3.
SAN DIEGO – Daily hydroxyurea treatment for sickle cell disease is feasible, safe, and effective for children in sub-Saharan Africa, according to the results of a large open-label, phase 1-2, international trial.
Hydroxyurea was associated with reduced rates of malaria and other infections, resulting in improved survival, according to Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, the Democratic Republic of the Congo.
“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” Dr. Tshilolo said in a press conference at the annual meeting of the American Society of Hematology.
Use of hydroxyurea has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to the researchers.
Moreover, most of the data on the efficacy of hydroxyurea come from studies conducted in the United States, Europe, and other high-income settings, said the study’s senior author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center.
“Now that there’s data in an African setting, I think this will go a long way to advancing [hydroxyurea therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said in an interview.
In the study by Dr. Ware, Dr. Tshilolo, and their colleagues, 606 children in four sub-Saharan African countries completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data. The children, who were aged 1-10 years, were started at 15-20 mg/kg of hydroxyurea for 6 months, followed by escalation to the maximum tolerated dose.
With a median of 2.5 years of treatment, treated children experienced less pain and anemia, fewer cases of malaria and other infections, and lower rates of transfusions and death versus rates observed in the pretreatment screening phase of the trial.
The rate of vasoocclusive pain during hydroxyurea treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio, 0.45; 95% confidence interval, 0.37-0.56), according to data simultaneously published in the New England Journal of Medicine.
Malaria infection rates were 22.9 events per 100 patient-years in the hydroxyurea treatment period versus 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66). Rates of nonmalaria infections were 90.0 events per 100 patient-years in the hydroxyurea treatment period versus 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).
Dr. Tshilolo said investigators were “encouraged” by the reduced infection rates, particularly in light of previous concerns that hydroxyurea could suppress the immune system and put children at risk for malaria.
Death rates were 1.1 per 100 patient-years in the hydroxyurea group and 3.6 per 100 patient-years in the pretreatment period (IR, 0.30; 95% CI, 0.10-0.88). Dose-limiting toxic events occurred in 5.1% of the children, which was below the protocol-specified threshold for safety, Dr. Tshilolo added.
Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the NIH/NHLBI and Bristol-Myers Squibb.
SOURCE: Tshilolo L et al. ASH 2018, Abstract 3.
REPORTING FROM ASH 2018
Key clinical point: Daily hydroxyurea treatment in sub-Saharan African children with sickle cell disease is feasible, safe, and effective, and has the additional benefit of reducing their rates of malaria and nonmalaria infections.
Major finding: Malaria infection rates were 22.9 versus 46.9 events per 100 patient-years in the hydroxyurea treatment period and pretreatment period, respectively (incidence rate ratio, 0.49; 95% CI, 0.37-0.66).
Study details: A phase 1-2, international, open-label trial including 606 children in four sub-Saharan African countries who completed a 2-month pretreatment screening phase and went on to receive hydroxyurea.
Disclosures: Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the NIH/NHLBI and Bristol-Myers Squibb.
Source: Tshilolo L et al. ASH 2018, Abstract 3.
Flipping the fetal hemoglobin switch reverses sickle cell symptoms
SAN DIEGO – Researchers were able to “flip the switch” from the adult to fetal form of hemoglobin using autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.
The advance was announced by investigators at the Dana-Farber Cancer Institute and Boston Children’s Hospital at the annual meeting of the American Society of Hematology. At 6 months of follow-up, one adult patient in the proof-of-concept study has experienced a reversal of the sickle cell phenotype, with no pain episodes or respiratory or neurologic events.
The fetal form of hemoglobin is known to be protective against the signs and symptoms of sickle cell disease, but apart from a few rare exceptions, people with the disorder begin to experience debilitating symptoms as levels of the fetal form begin to decline in early childhood and levels of the adult form of hemoglobin steadily rise.
In this video interview, Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, describes the novel approach of using RNA interference to knock down a repressor that suppresses expression of gamma globin in sickle cell disease.
SAN DIEGO – Researchers were able to “flip the switch” from the adult to fetal form of hemoglobin using autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.
The advance was announced by investigators at the Dana-Farber Cancer Institute and Boston Children’s Hospital at the annual meeting of the American Society of Hematology. At 6 months of follow-up, one adult patient in the proof-of-concept study has experienced a reversal of the sickle cell phenotype, with no pain episodes or respiratory or neurologic events.
The fetal form of hemoglobin is known to be protective against the signs and symptoms of sickle cell disease, but apart from a few rare exceptions, people with the disorder begin to experience debilitating symptoms as levels of the fetal form begin to decline in early childhood and levels of the adult form of hemoglobin steadily rise.
In this video interview, Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, describes the novel approach of using RNA interference to knock down a repressor that suppresses expression of gamma globin in sickle cell disease.
SAN DIEGO – Researchers were able to “flip the switch” from the adult to fetal form of hemoglobin using autologous stem cells genetically modified to simultaneously induce the fetal form of hemoglobin and decrease sickle hemoglobin.
The advance was announced by investigators at the Dana-Farber Cancer Institute and Boston Children’s Hospital at the annual meeting of the American Society of Hematology. At 6 months of follow-up, one adult patient in the proof-of-concept study has experienced a reversal of the sickle cell phenotype, with no pain episodes or respiratory or neurologic events.
The fetal form of hemoglobin is known to be protective against the signs and symptoms of sickle cell disease, but apart from a few rare exceptions, people with the disorder begin to experience debilitating symptoms as levels of the fetal form begin to decline in early childhood and levels of the adult form of hemoglobin steadily rise.
In this video interview, Erica B. Esrick, MD, from the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, describes the novel approach of using RNA interference to knock down a repressor that suppresses expression of gamma globin in sickle cell disease.
REPORTING FROM ASH 2018
Your guide to ASH 2018: Abstracts to watch
With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.
Lymphomas
Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.
The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.
Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.
In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).
Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).
Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).
Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.
“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
CAR T-cell therapy
There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).
“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.
The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).
Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.
The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.
The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).
Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
MDS/MPN
Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).
The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.
“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.
The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).
Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.
“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.
The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.
“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.
The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
AML
For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.
In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.
“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”
The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).
Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.
“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”
The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).
Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.
The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
Notable posters
Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.
Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.
How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.
You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.
Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.
With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.
Lymphomas
Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.
The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.
Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.
In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).
Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).
Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).
Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.
“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
CAR T-cell therapy
There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).
“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.
The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).
Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.
The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.
The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).
Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
MDS/MPN
Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).
The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.
“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.
The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).
Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.
“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.
The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.
“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.
The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
AML
For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.
In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.
“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”
The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).
Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.
“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”
The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).
Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.
The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
Notable posters
Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.
Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.
How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.
You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.
Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.
With more than 3,000 scientific abstracts at the 2018 annual meeting of the American Society of Hematology, it can be tough to figure out what research is most relevant to practice. But the editorial advisory board of Hematology News is making it easier this year with their picks for what to watch and why.
Lymphomas
Brian T. Hill, MD, of the Cleveland Clinic, offered his top picks in lymphoma research. Results of the phase 3 international Alliance North American Intergroup Study A041202 will be presented during the ASH plenary session at 2 p.m. PT on Sunday, Dec. 2 in Hall AB of the San Diego Convention Center (Abstract 6). The study compared bendamustine plus rituximab with ibrutinib and the combination of ibrutinib plus rituximab to see if the ibrutinib-containing therapies would have superior progression-free survival (PFS) in chronic lymphocytic leukemia (CLL), compared with chemoimmunotherapy. Results indicate that ibrutinib had superior PFS in older patients with CLL and could be a standard of care in this population.
The study is worth watching because it is the first report of a head-to-head trial of chemotherapy versus ibrutinib for first-line treatment of CLL, Dr. Hill said.
Two more studies offer important reports of “real world” experiences with chimeric antigen receptor (CAR) T-cell therapy.
In one multicenter retrospective study, researchers evaluated the outcomes of axicabtagene ciloleucel (axi-cel) CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when it is used a standard care. The researchers will report that 30-day responses in the real-world setting were comparable to the best responses seen in the ZUMA-1 trial. The full results will be reported at 9:30 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 91).
Another retrospective analysis looked at the use of axi-cell and revealed some critical differences from ZUMA-1, specifically the overall response rate (ORR) and complete response (CR) rate were lower than those reported in the pivotal clinical trial. The findings will be reported at 9:45 a.m. PT on Saturday, Dec. 1 in Pacific Ballroom 20 of the Marriott Marquis San Diego Marina (Abstract 92).
Researchers will also present the unblinded results from the ECHELON-2 study, which compared the efficacy and safety of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) versus standard CHOP for the treatment of patients with peripheral T-cell lymphoma. The results will be presented at 6:15 p.m. PT on Monday, Dec. 3 in room 6F of the San Diego convention center (Abstract 997).
Previously reported blinded pooled data showed that the treatment was well tolerated with 3-year PFS of 53% and OS of 73%.
“This should be a new standard of care for T-cell lymphomas,” Dr. Hill said.
CAR T-cell therapy
There are a number of abstracts featuring the latest results on CAR T-cell therapy. Helen Heslop, MD, of Baylor College of Medicine, Houston, recommended an updated analysis from the ELIANA study, which looked at the efficacy and safety of tisagenlecleucel in for children and young adults with relapsed/refractory acute lymphoblastic leukemia (ALL).
“Longer-term follow-up of the ELIANA study shows encouraging remission-duration data in pediatric and young adults with ALL without additional therapy,” Dr. Heslop said.
The findings will be presented at 4:30 p.m. PT on Monday, Dec. 3 in room 6A at the San Diego Convention Center (Abstract 895).
Another notable presentation will feature results from a phase 1B/2 trial evaluating infusion of CAR T cells targeting the CD30 molecule and encoding the CD28 endodomain (CD30.CAR-Ts) after lymphodepleting chemotherapy in patients with relapsed or refractory CD30+ Hodgkin lymphoma and non-Hodgkin lymphoma.
The researchers will report that there was a significant PFS advances for who received the highest dose level of the CAR T treatment, combined with bendamustine and fludarabine.
The study will be presented at 11 a.m. PT on Monday, Dec. 3 in room 6F at the San Diego Convention Center (Abstract 681).
Dr. Heslop also recommends another study being presented in the same session, which also shows encouraging results with CD30.CAR-Ts. Dr. Heslop is one of the co-investigators on the phase 1 RELY-30 trial, which is evaluating the efficacy of CD30.CAR-Ts after lymphodepleting chemotherapy. Preliminary results suggest a substantial improvement in efficacy. The findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in room 6F of the San Diego Convention Center (Abstract 680).
MDS/MPN
Vikas Gupta, MD, of Princess Margaret Cancer Center in Toronto, highlighted three abstracts to watch in the areas of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN).
The phase 3 Medalist trial is a randomized double-blind placebo controlled study of luspatercept to treatment anemia in patients with MDS with ring sideroblasts who require red blood cell transfusion. The researchers will report significantly reduced transfusion burdens for luspatercept, compared with placebo.
“This is a practice-changing, pivotal trial in the field of MDS for the treatment of anemia,” Dr. Gupta said.
The findings will be presented at 2 p.m. PT on Sunday, Dec. 2 during the plenary session in Hall AB in the San Diego Convention Center (Abstract 1).
Also during the Sunday plenary session is a presentation on MPN therapy (Abstract 4). Researchers will present data on secreted mutant calreticulins as rogue cytokines trigger thrombopoietin receptor (TpoR) activation, specifically in CALR-mutated cells.
“This study investigates in to the mechanistic oncogenetic aspects of mutant calreticulin, and has potential for therapeutic approaches in the future,” Dr. Gupta said.
The ASH meeting will also feature the final analysis of the MPN-RC 112 consortium trial of pegylated interferon alfa-2a versus hydroxyurea for the treatment of high-risk polycythemia vera (PV) and essential thrombocythemia (ET). The researchers will report that the CR rates at 12 and 24 months were similar in patients treated with pegylated interferon alfa-2a and hydroxyurea, but pegylated interferon alfa-2a was associated with a higher rate of serious toxicities.
“There is a continuous debate on optimal first-line cytoreductive therapy for high risk PV/ET, and this is one of the first randomized study to answer this question,” Dr. Gupta said.
The findings will be presented at 7 a.m. PT on Monday, Dec. 3 in Grand Hall D at the Manchester Grand Hyatt San Diego (Abstract 577).
AML
For attendees interested in the latest developments in acute myeloid leukemia, Thomas Fischer, MD, of Otto-von-Guericke-University Magdeburg (Germany), highlighted three don’t-miss sessions.
In an analysis of a large cohort of FLT3-ITD mutated AML patients in the RATIFY trial, researchers looked at the prognostic impact of ITD insertion site.
“Interestingly, in this large cohort of 452 FLT3-ITD mutated AML, the negative prognostic impact of beta1-sheet insertion site of FLT3-ITD could be confirmed,” Dr. Fischer said. “Further analysis of a potential predictive effect on outcome of midostaurin treatment is ongoing and will be very interesting.”
The findings will be presented at 5 p.m. PT on Sunday, Dec. 2 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 435).
Another notable presentation features results from the phase 2 RADIUS trial, a randomized study comparing standard of care, with and without midostaurin, after allogeneic stem cell transplant in FLT3-ITD–mutated AML.
“Here, efficacy and toxicity of midostaurin was investigated in a [minimal residual disease] situation post-alloSCT,” Dr. Fischer said. “Interestingly, adding midostaurin to standard of care reduced the risk of relapse at 18 months post-alloSCT by 46%.”
The complete findings will be presented at 10:45 a.m. PT on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 662).
Dr. Fischer singled out another study looking at the efficacy and safety of single-agent quizartinib in patients with FLT3-ITD mutated AML. In this large, randomized trial the researchers noted a significant improvement in CR rates and survival benefit with the single agent FLT3 inhibitors, compared with salvage chemotherapy for patients with relapsed/refractory mutated AML.
The findings will be presented at 8 a.m. on Monday, Dec. 3 in Seaport Ballroom F at the Manchester Grand Hyatt San Diego (Abstract 563).
Notable posters
Iberia Romina Sosa, MD, PhD, of Baylor College of Medicine in Houston, suggested several posters worth visiting in the areas of thrombosis and bleeding.
Poster 1134 looks at the TNF-alpha driven inflammation and mitochondrial dysfunction in the platelet hyperreactivity of aging and MPN.
How do you know if your therapy for thrombotic thrombocytopenic purpura is working? Poster 3736 examines the measurement of cell-derived microparticles as a possible tool to monitor response to therapy.
You don’t have to be taking aspirin to have a bleeding profile characteristic with consumption of a cyclooxygenase inhibitor. Poster 1156 provides a first report of a platelet function disorder caused by autosomal recessive inheritance of PTGS1.
Poster 2477 takes a closer look at fitusiran, an antithrombin inhibitor, which improves thrombin generation in patients with hemophilia A or B. Protocol amendments for safety monitoring move fitusiran to phase 3 trials, Dr. Sosa said.
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.