Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study

Authors

David A Sallman
Monzr M Al Malki
Adam S Asch
Eunice S Wang
Joseph G Jurcic
Terrence J Bradley
Ian W Flinn
Daniel A Pollyea
Suman Kambhampati
Tiffany N Tanaka
Joshua F Zeidner
Guillermo Garcia-Manero
Deepa Jeyakumar
Rami Komrokji
Jeffrey Lancet
Hagop M Kantarjian
Lin Gu
Yajia Zhang
Anderson Tan
Mark Chao
Carol O'Hear
Giridharan Ramsingh
Indu Lal
Paresh Vyas
Naval G Daver

Publication Date

5-20-2023

Journal

Journal of Clinical Oncology

Abstract

Purpose: Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479).

Patients and methods: Patients with previously untreated Revised International Prognostic Scoring System intermediate-/high-/very high-risk MDS received magrolimab intravenously as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg once-weekly or once-every-2-week maintenance dose. Azacitidine 75 mg/m2 was administered intravenously/subcutaneously once daily on days 1-7 of each 28-day cycle. Primary end points were safety/tolerability and complete remission (CR) rate.

Results: Ninety-five patients were treated. Revised International Prognostic Scoring System risk was intermediate/high/very high in 27%, 52%, and 21%, respectively. Fifty-nine (62%) had poor-risk cytogenetics and 25 (26%) had TP53 mutation. The most common treatment-emergent adverse effects included constipation (68%), thrombocytopenia (55%), and anemia (52%). Median hemoglobin change from baseline to first postdose assessment was -0.7 g/dL (range, -3.1 to +2.4). CR rate and overall response rate were 33% and 75%, respectively. Median time to response, duration of CR, duration of overall response, and progression-free survival were 1.9, 11.1, 9.8, and 11.6 months, respectively. Median overall survival (OS) was not reached with 17.1-month follow-up. In TP53-mutant patients, 40% achieved CR with median OS of 16.3 months. Thirty-four patients (36%) had allogeneic stem-cell transplant with 77% 2-year OS.

Conclusion: Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ClinicalTrials.gov identifier: NCT04313881 [ENHANCE]).

Keywords

Humans, Azacitidine, Myelodysplastic Syndromes, Antibodies, Monoclonal, Humanized, Progression-Free Survival, Leukemia, Myeloid, Acute, Treatment Outcome

DOI

10.1200/JCO.22.01794

PMID

36888930

PMCID

PMC10414740

PubMedCentral® Posted Date

3-8-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes