Evaluating the Combination of Anti-CD47 Antibodies and HMAs for Higher-Risk MDS

According to a poster at the 2022 American Society of Clinical Oncology, the combination of the anti-CD47 monoclonal antibody, magrolimab, with azacitidine was well-tolerated and demonstrated promising efficacy in patients with untreated higher-risk myelodysplastic syndromes (MDS). The phase 1b study was led by David Andrew Sallman, MD, from the Moffitt Cancer Center in Tampa, FL.

In a cohort of 95 patients with untreated intermediate-, high-, or very-high-risk MDS, Dr. Sallman and colleagues administered a priming dose of intravenous magrolimab 1 mg/kg, followed by a ramp-up to a maintenance dose 30 mg/kg once weekly or every other week. The primary measures of the study were safety, tolerability, and the rate of complete remission (CR).

Among the patients, 27%, 52%, and 21% had intermediate, high, or very-high IPSS-R risk. Additionally, 22% had therapy-related MDS, 26% had a TP53 mutation, and 62% had poor-risk cytogenetics. The rate of mortality at 60 days was 2%, the rate of CR was 33%, and the rate of objective response was 75%. According to the investigators, the median time to first OR, duration of CR, duration of OR, and progression-free survival (PFS) was 1.9, 11.1, 9.8, and 11.6 months, respectively.

The most commonly reported treatment-emergent adverse events (TEAEs) included constipation (68%), thrombocytopenia (55%), anemia (52%), neutropenia (47%), nausea (46%), and diarrhea (44%). Grade III and IV TEAEs included anemia (47%), neutropenia (46%), thrombocytopenia (46%), and white blood cell count decrease (30%).

Ultimately, the authors presented their data in support of the use of magrolimab with azacitidine in patients with treatment-naïve higher-risk MDS. For further reference, they pointed to the ongoing phase III ENHANCE trial on magrolimab or placebo with azacitidine.