Magrolimab and Azacitidine Combination Treatment for Patients With Untreated High-Risk MDS

Results from a Phase 1b Trial

According to findings from a phase 1b trial recently published in the Journal of Clinical Oncology, magrolimab and azacitidine combination treatment yielded safe and effective results among patients with untreated high-risk myelodysplastic syndromes (MDS). 

According to David Sallman, MD, Moffitt Cancer Center, Tampa, Florida, and coauthors, results of previous studies have indicated that “magrolimab + azacitidine increased phagocytosis in vitro and in vivo in myeloid models,” which provides “strong mechanistic rationale for investigating the combination in patients” further in the present study. 

Dr Sallman et al aimed to reach primary endpoints of risk of adverse events and complete response rate, as well as secondary endpoints including overall survival, minimal residual disease (MRD) negativity, cytogenetics, and the identification of TP53 and/or other prespecified mutations. 

95 adult patients with untreated MDS and an IPSS-R risk category ≥ intermediate and a median age of 69 years were enrolled in this study.  Patients received a priming dose of magrolimab at 1 mg/kg, followed by a maintenance dose of either 30 mg/kg once a week or once every 2 weeks. Patients received azacitidine at 75 mg/m2 once daily on days 1 through 7 of each cycle of 28 days. Treatment was continued until toxicity, progression, or death occurred. 

Safety results indicated that poor-risk cytogenetics were observed in 62% of patients, and TP53 mutation was present in 26% of patients (n=25). The most common treatment-related adverse events were constipation (68.4%), thrombocytopenia (54.7%), anemia (51.6%), neutropenia (47.4%), nausea (46.3%), and diarrhea (43.2%). Serious adverse events were observed in ≥ 5% of patients and included febrile neutropenia (24.2%), pneumonia (9.5%), anemia (8.4%), bacteremia (6.3%), and pyrexia (5.3%). Treatment-related adverse events resulted in treatment discontinuation in 10 patients total. 

The complete response rate was 33% and the overall response rate was 75%, respectively. The median time to respond was 1.9 months. The median progression-free survival was 11.6 months. The median overall survival was unable to be reached at the 17.1-month follow-up. 40% of TP53 mutated patients achieved complete response with a median overall survival of 16.3 months. 36% of patients (n=34) underwent allogeneic stem-cell transplantation with a 77% 2-year overall survival. 

In conclusion, the results of this study demonstrate the safety and efficacy of the combination of magrolimab and azacitidine among patients with previously untreated high-risk MDS, including those with TP53 mutations. 

Dr Sallman et al added, “The combinations of magrolimab + azacitidine and placebo + azacitidine are being evaluated in patients with [high-risk]-MDS in the multinational, randomized phase 3 ENHANCE trial, which is recruiting as of this report. If successful, this combination could be an important addition for patients with HR-MDS, a population of significant unmet need.” 

Source: 

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 [published online ahead of print, 2023 Mar 8]. J Clin Oncol. 2023; JCO2201794. doi:10.1200/JCO.22.01794