1. Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study.
- Author
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Sallman, David, Al Malki, Monzr, Asch, Adam, Wang, Eunice, Jurcic, Joseph, Bradley, Terrence, Flinn, Ian, Pollyea, Daniel, Kambhampati, Suman, Tanaka, Tiffany, Zeidner, Joshua, Garcia-Manero, Guillermo, Jeyakumar, Deepa, Komrokji, Rami, Lancet, Jeffrey, Kantarjian, Hagop, Gu, Lin, Zhang, Yajia, Tan, Anderson, Chao, Mark, OHear, Carol, Ramsingh, Giridharan, Lal, Indu, Vyas, Paresh, and Daver, Naval
- Subjects
Humans ,Azacitidine ,Myelodysplastic Syndromes ,Antibodies ,Monoclonal ,Humanized ,Progression-Free Survival ,Leukemia ,Myeloid ,Acute ,Treatment Outcome - Abstract
PURPOSE: Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a dont-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]).
- Published
- 2023