The annual meeting of the American Society of Hematology was held virtually this year from Dec. 5 to 8 and attracted participants from around the world, including hematology specialists as well as clinical practitioners and other health care professionals. The conference featured presentations focusing on the diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems.
In one study, Haydar Frangoul, M.D., of Children’s Hospital at TriStar Centennial in Nashville, Tennessee, and colleagues found that gene editing using CRISPR-Cas9 is safe and feasible and can provide clinical benefit to patients with sickle cell disease and transfusion-dependent ß-thalassemia.
The authors collected peripheral blood stem cells that were shipped to a manufacturing facility to be gene edited. The patients underwent chemotherapy prior to receiving their gene-edited stem cells, similar to a patient undergoing an autologous blood and marrow transplant. The researchers found that gene editing using CRISPR-Cas9 to target the BCL11A in the erythroid cells resulted in stable and sustained engraftment.
“This has resulted in definite benefit for the seven patients with ß-thalassemia, making them transfusion-independent, and for the three patients with sickle cell disease who remain without symptoms of vaso-occlusive crisis,” Frangoul said. “These results are exciting and give hope to patients with ß-thalassemia and sickle cell disease. Additional patients and longer follow-up are needed to confirm these findings.”
Several authors disclosed financial ties to the pharmaceutical, medical device, and biotechnology industries.
Abstract No. 4
In the phase 3 Health Outcomes with Padua gene; Evaluation in Hemophilia B (HOPE-B) study, Steven Pipe, M.D., of the University of Michigan in Ann Arbor, and colleagues found that a single dose of etranacogene dezaparvovec, an investigational gene therapy for hemophilia B (HB), provides effective transduction in HB patients, including patients who have antibody titers as high as 678.
The authors evaluated the use of etranacogene dezaparvovec, a gene therapy that uses an adeno-associated virus vector that has viral genes replaced with a functional copy of the human factor IX gene, which has been enhanced by a naturally occurring point mutation that codes for a hyperactive form of factor IX. This boosts the effective activity of factor IX in the blood plasma by six- to eightfold. The vector is delivered as a single intravenous infusion in the outpatient setting, and within a couple of weeks, factor IX expression is sufficient to protect from bleeding. The researchers found that participants achieved a mean factor IX activity of 37 percent 26 weeks following dosing (with nonhemophilic range starting at 40 percent). Levels remained stable over the course of the study, with the longest follow-up being 18 months. These levels allowed the patients who achieved transduction to cease prophylaxis for the duration of the follow-up period. The number of treated bleeds fell by 91 percent compared with a six-month lead-in period when all patients were on prophylactic factor IX infusions.
“This study is the first phase 3 study to report findings on an entire cohort of subjects. It is also the largest cohort of subjects to receive gene therapy for hemophilia, to date,” Pipe said. “This looks to be a transformative therapy for patients — looks to be an option for patients across the adult lifespan. Our patient population has been looking forward to a one-time therapy like this that could provide lasting protection from bleeds.”
Several authors disclosed financial ties to pharmaceutical companies, including uniQure, the manufacturer of etranacogene dezaparvovec.
Abstract No. LBA-6
William A. Wood, M.D., M.P.H., of the University of North Carolina in Chapel Hill, and colleagues found that patients with hematologic cancers are especially vulnerable to COVID-19 infection and that the risk within this population is unevenly distributed.
The authors used a voluntary data collection registry for which providers or sites caring for patients with hematologic malignancies and COVID-19 infection submitted deidentified data via an online data collection platform. The researchers found that 20 percent of patients with blood cancers who had COVID-19 infection died, including 33 percent of those who required hospital or intensive care unit-level care.
“The risk of dying was highest in patients who were older, had more severe infection, opted to forgo more intensive treatment, and/or had poorer prognosis before their COVID-19 infection, as determined by their treating clinicians,” Wood said. “Because patients with blood cancers are medically vulnerable, we think it is important for these patients and for the health care system to continue to take appropriate precautions to limit the risk of acquiring COVID-19.”
Several authors disclosed financial ties to the pharmaceutical, medical device, and biotechnology industries.
Abstract No. 215
ASH: CRISPR-Cas9 Gene Editing Promising in TDT, SCD
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