Magrolimab Shows Antitumor Activity in AML Ineligible for Intensive Chemotherapy

Results from a phase 1b trial published in the Journal of Clinical Oncology suggested that the addition of magrolimab, an CD47 antibody, to azacitidine showed antitumor effects and was well tolerated among patients with previously untreated acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy.

Notably, the rates of complete response (CR) were similar among patients with and without a TP53 mutation.

This multicenter, open-label trial (ClinicalTrials.gov Identifier: NCT03248479) treated 87 patients with previously untreated AML with magrolimab plus azacitidine. The primary endpoints were safety and CR rate.

At baseline, the median age was 73 and 42.5% of patients were female. There were 86.2% of patients who were White, 4.6% who were Asian, 3.4% who were Black or African American, and 5.7% whose race/ethnicity was not reported or missing.

The majority of patients had an Eastern Cooperative Oncology Group performance status of 1. There were 69.0% of patients with adverse cytogenetic risk and 82.8% with a TP53 mutation. There were 6.9% of patients with an IDH1 or IDH2 mutation and 2.3% with a FLT3 mutation.

The objective response rate was 47.1%, with 32.2% of patients achieving a CR, including 5.7% with a CR with incomplete blood count recovery and 33.3% with a CR with full or partial hematologic recovery. The duration of response was a median of 8.7 months.

Of the patients with a TP53 mutation, the ORR was 47.2% and 31.9% achieved a CR. The duration of response was 7.7 months.

The median overall survival (OS) for the entire cohort was 10.8 months, with a median of 18.9 months among patients who had TP53 wild-type disease and 9.8 months among patients with a TP53 mutation. The event-free survival was 3.7 months overall, and 2.9 and 3.7 months among patients with wild-type or mutated TP53.

There were 6 grade 5 treatment-emergent adverse events (TEAEs) due to pneumonia, febrile neutropenia, hypoxia, or pleural effusion. The most common magrolimab-related TEAEs included infusion-related reactions and fatigue. Magrolimab dose modifications included 1.1% of patients who received a dose reduction and 46.0% who required a dose delay.

“Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations,” the authors concluded in their report.

This trial has since been closed due to futility in a preplanned analysis of the phase 3 ENHANCE trial. The phase 3 ENHANCE-2 and ENHANCE-3 trials, in which magrolimab is combined with azacitidine and venetoclax, remain active and ongoing.

Disclosures: This study was supported by Gilead Sciences, Inc. Please see the original reference for a full list of disclosures.

Reference
Daver NG, Vyas P, Kambhampati S, et al. Tolerability and efficacy of the anticluster of differentiation 47 antibody magrolimab combined with azacitidine in patients with previously untreated AML: phase Ib results. J Clin Oncol. Published online September 13, 2023. doi: 10.1200/JCO.22.02604

This article originally appeared on Hematology Advisor