Magrolimab Plus Azacitidine Shows Promising Efficacy in Newly Diagnosed Higher-Risk MDS

HOUSTON — A phase Ib trial indicated that the combination of magrolimab and azacitidine was well tolerated and resulted in an objective response rate of 75% in patients with higher-risk myelodysplastic syndromes (MDS), a disease that currently has a high unmet treatment need.

David Sallman, MD, of the Moffitt Cancer Center in Tampa, Florida, discussed the findings during the Society of Hematologic Oncology (SOHO) Annual Meeting.

Azacitidine is the current standard of care for higher-risk MDS, and magrolimab is a monoclonal antibody blocking CD47 expression.

The study included 95 patients with untreated higher-risk MDS who received magrolimab 1 mg/kg intravenously for a priming dose, followed by a 30 mg/kg maintenance dose once a week or every two weeks, plus azacitidine 75 mg/m² intravenously or subcutaneously on days one to seven of each 28-day cycle.

The median patient age was 69 years (range, 28-91 years), and more than half (52%) had high-risk disease per the Revised International Prognostic Scoring System. A total of 22% of patients had therapy-related MDS, 26% had TP53-mutated disease, and 62% had poor-risk cytogenetics. Patients received a median of six treatment cycles (range, 1-27 cycles).

The most common treatment-related adverse events were constipation (68%), thrombocytopenia (55%), anemia (52%), neutropenia (47%), nausea (46%), and diarrhea (43%). The most common grade 3/4 adverse events were anemia (47%), neutropenia (46%), thrombocytopenia (46%), and decreased white blood cell count (30%). Six patients discontinued the regimen due to adverse events.

The 60-day mortality rate was 2%, and median hemoglobin change from baseline after the first treatment dose was ‒0.7 g/dL (range, ‒3.1 to 2.4 g/dL).

A third of patients (33%) experienced a complete remission (CR; co-primary endpoint). Median time to first objective response was 1.9 months, duration of CR was 11.1 months, duration of objective response was 9.8 months, and progression-free survival was 11.6 months. At 12 and 24 months, the overall survival rates were 75% and 52%, respectively. After 17.1 months of follow-up, median OS was not reached.

Among the 25 patients with TP53 mutations, the CR rate was 40%, and the median OS was 16.3 months. For those with wild-type TP53 mutations (n=61), the CR rate was 31%, and the median OS was not reached.

The phase III ENHANCE trial assessing magrolimab with or without azacitidine in this patient population is ongoing.

Reference

Sallman D, Al Malki M, Asch A, et al. Magrolimab in combination with azacitidine for patients with untreated higher-risk myelodysplastic syndromes (HR MDS): 5F9005 phase 1b study results. Abstract # MDS-445. Presented at the 2022 Society of Hematologic Oncology (SOHO) Annual Meeting, September 28-October 1, 2022.