Dr. Daver on the Tolerability of Magrolimab Plus Azacitidine in AML/MDS

Naval G. Daver, MD, an associate professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the tolerability of magrolimab (formerly Hu5F9 G4) plus azacitidine in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Initial data presented at the 2020 European Hematology Association Congress were on the MDS cohort, says Daver. A total of 29 patients were enrolled on the AML cohort, and 39 patients comprised the MDS cohort who were treated with the standard dose of azacitidine at 75 mg/m² on days 1 through 7.

Magrolimab has an interesting dosing schedule, according to Daver. Initially, the agent was given through intrapatient dose escalation in an effort to mitigate on-target anemia, a significant toxicity observed with this approach. CD47 is expressed heavily on the surface of red blood cells (RBCs), especially on older cells, according to Daver. When this type of approach is used, clearance of the older RBCs is achieved and the body compensates by producing younger cells, says Daver. Usually around day 12 to 14, once the full dose of magrolimab/azacitidine is given, anemia is no longer observed; this has been a consistent finding.

With regard to safety, no 60-day mortalities were reported with the combination. Only 1 patient discontinued treatment in the AML cohort because of an infusion reaction; the patient recovered within 24 hours, but decided not to proceed with treatment.

Overall, the safety profile of the combination was favorable that is comparable to that of azacitidine alone. No immune toxicities, such as significant neutropenia or thrombocytopenia, were reported. Notably, an improvement in neutropenia and thrombocytopenia was observed after 6 to 8 weeks on the study, concludes Daver.