The recent meeting of the American Society of Hematology took place in Atlanta, Georgia. It was a hybrid meeting, probably the largest of its kind since the onset of the pandemic, that included about 29,000 registrants, over 12,000 of whom attended the in-person meeting. The most notable feature of the meeting was that it took place under carefully developed protocols, allowing for in-person interaction among the attendees, while still supporting those who, by regulation or choice, were unable to attend.
Notable presentations included the impact of engineered cell therapy in the management of early-relapsed, or refractory nonHodgkin Lymphoma, establishing a new paradigm in the management of aggressive disease that may displace autologous transplant, the previous standard management tool. A group of international investigators conducted a phase 3 randomized trial of an autologous antiCD19 chimeric antigen receptor T-cell, axicabtagene ciloleucel, versus standard-of-care antineoplastic therapy and autologous hematopoietic transplant for patients with large B cell lymphoma refractory to, or relapsed within 12 months after initial chemoimmunotherapy. Patients assigned to the standard therapy could undergo CAR T-cell therapy off protocol. 359 patients were enrolled, most with disease refractory to initial therapy. After a median follow-up of two years, complete remission rates and the median event-free survival were significantly longer with axicabtagene therapy, and estimates of two-year event-free survival significantly were better for the group assigned to the engineered cell product. Grade 3 or greater adverse events and treatment-related deaths were similar in the two treatment arms. These favorable results were not confirmed, however, in another randomized trial of CAR-T cells, this time with the tisagenlecleucel product as compared to standard care for a similar group of patients. In the latter BELINDA study, about half the patients assigned to standard therapy crossed over to receive tisa-cel. A delay in receiving the tisacel infusions among those assigned to the investigational arm for 60-day response assessment, and the choice of platinum-based chemotherapy may have led to an equivalent event-free survival for the two groups.
Also of note were presentations of novel therapies for management of Sickle Cell Disease, and classical hemophilia. In the ATLAS-INH trial, a group of international investigators reported results of a phase 3 study conducted to evaluate the efficacy and safety of a small inhibitory RNA molecule, Fitusiran, targeting antithrombin in order to restore thrombin generation and rebalance hemostasis in patients with hemophilia with inhibitors. Patients randomized to the control arm received on-demand bypassing agents. Efficacy of Fitusiran prophylaxis treatment was achieved for primary and all secondary endpoints in both hemophilia A and hemophilia B patients demonstrating the efficacy of monthly subcutaneous prophylaxis with fitusiran in preventing hemorrhage.
Among the presentations were several oral sessions devoted to novel agents for the management of acute leukemia, multiple myeloma, myeloproliferative and myelodysplastic diseases that focused on immunotherapies and novel small-molecular therapy. There were sessions devoted to hematopoietic cell transplantation, and to novel therapies in nonmalignant hematologic disease. Scientific sessions also included studies in the biology of hematopoietic stem cells, and basic mechanisms of iron metabolism and coagulation disturbance. Prominent were sessions on the biology of the novel coronavirus, and its impact on disease management in Hematology. Among the basic science presentations was an abstract, presented during the scientific plenary session, describing a potential mechanism by with severe infection with SARS-CoV-2 might induce thrombophilia. In this presentation, investigators from Boston and New York evaluated the change in orientation of membrane phospholipids in endothelial cells by a viral protein that acts as a calcium channel. The expression of the viral protein, ORF3a resulted in enhanced expression of tissue-factor procoagulant activity through increased intracellular calcium levels that could be abrogated by inhibitors of the enzyme scramblase that reoriented distribution of membrane phosphotidyl serine. Potential mechanisms to target this axis were described.
Unique to the current meeting, there were also special sessions devoted to health disparities, and inequities in the delivery of healthcare in the Hematology space.
Dr. Schiller reports a variety of funding, including AbbVie, Amgen, Gilead, GSK, J&J, Novartis, Pfizer, and more.
Image by DrAfter123 / GettyImages