In a phase Ib study reported in the Journal of Clinical Oncology, Naval G. Daver, MD, and colleagues found that the combination of the anti-CD47 antibody magrolimab and azacitidine was active in previously untreated patients with acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy.
As stated by the investigators: “Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47 [CD47], an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab.”
Naval G. Daver, MD
Study Details
In the U.S. multicenter study, 87 patients enrolled between February 2018 and May 2021 received magrolimab at 1 mg/kg on days 1 and 4, followed by 15 mg/kg on day 8 and 30 mg/kg once weekly or every 2 weeks as maintenance, and azacitidine at 75 mg/m2 on days 1 to 7 of each 28-day cycle. A total of 72 patients (82.8%) had TP53 mutations. The primary efficacy outcome measure was complete remission rate.
Key Findings
Complete remission was achieved in 28 of 87 patients (32.2%, 95% confidence interval [CI] = 22.6%–43.1%), including 23 of 72 patients (31.9%, 95% CI = 21.4%–44.0%) with TP53 mutations and 5 of 15 patients (33.3%, 95% CI = 11.8%–61.6%) with wild-type TP53. Median durations of complete remission were 9.6 months (95% CI = 5.1–10.9 months), 7.6 months (95% CI = 4.7–9.7 months), and 31.3 months (95% CI = 18.7–31.3 months), respectively.
Overall, objective response rates were 47.1% among all patients, 47.2% among those with TP53 mutations, and 46.7% among those with wild-type TP53. Median response durations were 8.7 months (95% CI = 7.4–10.9 months), 7.7 months (95% CI = 6.5–10.1 months), and 18.7 months (95% CI = 5.7 months to not reached), respectively.
Median overall survival was 10.8 months (95% CI = 7.2–12.8 months) among all patients, 9.8 months (95% CI = 6.8–12.3 months) among patients with TP53 mutations, and 18.9 months (95% CI = 4.3 months to not reached) among those with wild-type TP53.
The most common adverse events of any grade among patients receiving the doublet were constipation (49%), nausea (49%), diarrhea (48%), and febrile neutropenia (43%). The most common grade 3 or 4 adverse events were thrombocytopenia (37%), anemia (35%), and febrile neutropenia (33%). The most common serious adverse events were febrile neutropenia (24%), pneumonia (13%), and infusion-related reactions (7.0%). Adverse events led to discontinuation of magrolimab in 30% of patients and azacitidine in 29%. Adverse events led to death in 18 patients (21%), with none considered related to treatment.
The investigators concluded: “Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier NCT04778397) and ENHANCE-3 (NCT05079230) studies are recruiting front-line patients with AML.”
Dr. Daver, of The University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Gilead Sciences. For full disclosures of the study authors, visit ascopubs.org.
