Magrolimab plus azacitidine demonstrated a durable response and an encouraging overall survival (OS) in the front-line setting in patients with TP53-mutated acute myeloid leukemia (AML) who were unsuitable for intensive therapy, according to findings from a phase Ib trial.
Magrolimab is a first-in-class, anti-CD47 monoclonal antibody and macrophage checkpoint inhibitor that blocks CD47. Previous research had demonstrated the ability of magrolimab to induce phagocytosis of tumor cells as well as synergistic effects when used in combination with azacitidine.
The single-arm trial enrolled 72 patients with TP53-mutated AML (median age, 73 years; range, 31-89 years). Primary endpoints were safety, tolerability, and complete remission (CR) as determined by the European LeukemiaNet 2017 criteria.
Patients received magrolimab intravenously starting with a priming dose of 1 mg/kg followed by ramp-up to 30 mg/kg once or twice weekly as maintenance. Azacitidine 75 mg/m2 was given intravenously or subcutaneously on days one through seven of each 28-day cycle.
The overall objective response rate was 48.6%. This included 33.3% of patients who experienced CR; 8.3% of patients experienced CR with incomplete hematologic recovery (CRi) or CR with partial hematologic recovery (CRh), 1.4% attained a morphologic leukemia-free state (MLFS), and 5.6% experienced partial remission.
Of the 31 evaluable patients who achieved CR, CRi, CRh, or MLFS, 14 (45.2%) achieved minimal residual disease negativity by flow cytometry.
The median time to CR/CRi was 2.2 months (range, 1.7-7.2 months) and to CR was 3.0 months (range, 1.8-9.6 months). The median duration of CR and CR/CRi were 7.7 months (range, 4.7-10.9 months) and 8.7 months (range, 5.3-10.9 months), respectively.
Median OS among all 72 patients was 10.8 months (range, 6.8-12.8 months), with a median follow-up of 8.3 months. The 30- and 60-day mortality rates were 8.3% and 18.1%, respectively.
Treatment was discontinued in 4.2% of patients due to treatment-emergent adverse events. The most common grade ≥3 treatment-related adverse events were febrile neutropenia, anemia, thrombocytopenia, pneumonia, and neutropenia. Lower-grade adverse events included constipation, diarrhea, nausea, fatigue, decreased appetite, peripheral edema, and cough.
“In high-risk frontline patients with TP53-mutated AML unsuitable for intensive chemotherapy, magrolimab [plus] azacitidine showed durable responses and encouraging OS in a single-arm study,” the authors concluded.
A phase III trial of magrolimab plus azacitidine versus standard of care in TP53-mutated AML is currently ongoing.
Daver N, Vyas P, Kambhampati S, et al. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline patients with TP53-mutated acute myeloid leukemia: phase 1b results. Abstract #S132. Presented at the 2022 European Hematology Association Congress, June 9-12, 2022.