Magrolimab in combination with azacitidine is well tolerated and shows promising efficacy in patients with higher-risk myelodysplastic syndrome (MDS), according to research published in the Journal of Clinical Oncology.
The findings are from a phase Ib study evaluating the safety and tolerability of magrolimab and azacitidine in patients with previously untreated higher-risk (Revised International Prognostic [IPSS-R] Scoring System intermediate-/high-/very high-risk) MDS (ClinicalTrials.gov Identifier: NCT03248479).
Patients received a priming dose (1 mg/kg) of magrolimab intravenously followed by ramp-up to a maintenance dose (30 mg/kg, once weekly or once every 2 weeks). They received azacitidine (75 mg/m2) intravenously or subcutaneously once daily on days 1-7 of each 28-day cycle. The primary endpoints were safety and complete remission (CR) rate.
A total of 95 patients (median age, 69 years; range, 28-91; 65.3% men and 34.7% women) were treated with the magrolimab in combination with azacitidine. According to the IPSS-R, 27% of patients had intermediate-risk MDS; 52% of patients high-risk MDS; and 21% of patients had very high-risk MDS. Poor-risk cytogenetics were identified in 62% and TP53 mutation in 26% of patients. The median exposure to the treatment was 6 cycles (range, 1-27).
The investigators reported that the most common treatment-emergent adverse effects were constipation (68%), thrombocytopenia (55%), and anemia (52%). They found a median hemoglobin change of -0.7 g/dL (range: -3.1 to +2.4) from baseline to first post-dose assessment.
In the intention-to-treat analysis, the team observed a CR rate of 32.6% and an objective response (OR) rate of 74.7%. In patients with TP53 mutation, they observed a CR of 40% and an OR rate of 68.0%.
“On the basis of the interim results from this phase Ib trial, the combinations of magrolimab + azacitidine and placebo + azacitidine are being evaluated in patients with [higher-risk] MDS in the multinational, randomized phase 3 ENHANCE trial, which is recruiting as of this report (ClinicalTrials.gov identifier: NCT04313881),” the authors wrote in their report. “If successful, this combination could be an important addition for patients with [higher-risk] MDS, a population of significant unmet need.”
Limitations of the study included the single-arm, nonrandomized design, lack of centralized next-generation sequencing assessment, and insufficient sample sizes to determine efficacy and outcomes in individual molecular subgroups.
Disclosure: This research was supported by Gilead Sciences, Inc. Please see the original reference for a full list of disclosures.
Sallman DA, Al Malki MM, Asch AS, et al. Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study. J Clin Oncol. Published online March 8, 2023. doi:10.1200/JCO.22.01794