By: Kerri Fitzgerald
A phase 1b/2 study found that the triplet combination of azacitidine, venetoclax, and magrolimab was safe for the treatment of acute myeloid leukemia (AML), though event-free and overall survival were not “promising,” according to Naval Daver, MD, of the University of Texas MD Anderson Cancer Center, and colleagues who published the results in Clinical Cancer Research.
The study included 54 adult patients (median age, 70.1 years) who were treated with the triplet combination in both the frontline and relapsed or refractory setting. Nearly two-thirds of patients (n=35; 64.8%) had TP53-mutated disease.
Patients received the following treatment:
- Azacitidine 75mg/m2 for 7 days
- Venetoclax 400 mg/day for 28 days
- Magrolimab at the following dose schedule:
- Cycle one: 1 mg/kg on days 1 and 4; 15 mg/kg on day 8; 30 mg/kg on days 11, 15, and 22
- Cycle two: 30 mg/kg weekly
- Cycle three and beyond: 30 mg/kg every 2 weeks
Composite complete response (CRc) occurred in 34 patients (63%), including in 49% with TP53-mutated disease and 90% with TP53 wild-type.
At a median follow-up of 27.9 months, median event free survival (EFS) and overall survival (OS) were:
- Overall: 6.6 months and 9.8 months, respectively
- In TP53-mutated patients: 5.9 and 7.6 months, respectively
- In TP53 wild-type patients: 9.6 months and 13.0, months, respectively
In relapsed or refractory patients (n=52), CRc was 29% and median OS was 3.9 months.
The most common grade ≥3 adverse event was infections (75.4%). There was no immune-mediated toxicity or deaths related to therapy.
“Gene set enrichment analysis revealed enrichment of IFNγ and TNFα signaling in non-responders at baseline, while erythroid differentiation was associated with resistance,” the researchers noted.
Reference
Daver N, Senapati J, Kantarjian HM, et al. Azacitidine, venetoclax and magrolimab in newly diagnosed and relapsed refractory acute myeloid leukemia: phase 1b/2 study and correlative analysis. Clin Cancer Res. 2025. doi:10.1158/1078-0432.CCR-25-0229
