ASH 2020: Early Results in Targeting CD47 in AML
Posted: Tuesday, December 8, 2020
Magrolimab, an antibody targeting the macrophage immune checkpoint CD47, appears to be well tolerated when combined with azacitidine in patients with acute myeloid leukemia (AML). This combination therapy produced no reported immune-related adverse events, with activity noted in wild-type and mutant TP53 cancers. These data were presented by David A. Sallman, MD, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, at the 2020 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 330).
This phase IB trial recruited 52 patients with AML who had not yet initiated therapy. Most (64%) patients had poor-risk cytogenetics, and 65% of patients had mutations in TP53. The patients were administered a magrolimab priming/dose-escalation regimen intravenously (to mitigate on-target anemia) and azacitidine.
At the time of data cutoff, 34 patients were evaluable for efficacy. A total of 22 patients (65%) achieved an objective response, including 14 with complete remission, 4 with complete remission and incomplete cell count recovery, 1 with a partial response, 11 with stable disease, and 1 with progressive disease. The time to response was a median of 2.04 months. Among the patients with abnormal cytogenetics at the time of enrollment, 47% achieved a cytogenetic complete response.
For the 21 patients with mutated TP53, 48% achieved a complete response, and 19% achieved a complete response with incomplete cell count recovery. The median duration of response was 9.9 months, and 89% continued to respond at 6 months. The median overall survival in patients with mutated and wild-type TP53 was 12.9 months and 18.9 months, respectively. In addition, bone marrow leukemia stem cells were eliminated by this regimen in 71% of all responding patients.
The treatment regimen was well tolerated overall, with a similar safety profile to azacitidine monotherapy. Common treatment-related adverse events included anemia, fatigue, increased serum bilirubin levels, neutropenia, thrombocytopenia, and nausea. On-target anemia was transient and reversible. There were no observed grade 4 or 5 adverse events or immune-related adverse events associated with magrolimab alone.
Disclosure: For full authors’ disclosures, visit ash.confex.com.