Combination magrolimab, azacitidine, and venetoclax is effective in patients with newly diagnosed acute myeloid leukemia (AML) but not in patients with relapsed/refractory AML, according to a presentation at the 2022 ASH Annual Meeting.
The complete remission (CR) rate was 49% in patients with newly diagnosed AML and 19% in patients with relapsed/refractory disease.
This phase 1/2 trial (ClinicalTrials.gov Identifier: NCT04435691) included 43 patients who received magrolimab, azacitidine, and venetoclax in the frontline setting and 36 who had relapsed/refractory disease at baseline.
Patients received azacitidine at 75 mg/m2 on days 1-7 and venetoclax at 400 mg daily on days 1-28. The recommended phase 2 dose of magrolimab was 1 mg/kg on days 1 and 4 of cycle 1, 15 mg/kg on day 8 of cycle 1, and 30 mg/kg on days 11, 15, and 22 of cycle 1. The drug was given at 30 mg/kg weekly in cycle 2 and every other week in cycle 3 and beyond.
Results in the Frontline Setting
In the frontline cohort, the median age was 70 (range, 32-84) years, 37% of patients were women, 93% had an ECOG performance status of 1-2, and 91% had adverse cytogenetics. Most patients (n=33) had de novo AML, and 22 of these patients had mutated TP53. The remaining 10 patients had secondary AML, and half of them had mutated TP53.
The CR rate was 49% in the overall cohort. Among patients with de novo AML, the CR rate was 46% in patients with mutated TP53 and 55% in those with wild-type TP53. Among patients with secondary AML, the CR rates were 40% and 60%, respectively.
Among patients with de novo AML, the median follow-up was 14.5 months. The median duration of response was not reached regardless of TP53 status. The 12-month overall survival (OS) rate was 83% in patients with wild-type TP53 and 53% in patients with TP53 mutations.
Among patients with secondary AML, the median follow-up was 14.0 months. The median duration of response was 5.9 months in patients with TP53 mutations and 2.2 months in patients with wild-type TP53. The median OS was 7.6 months and 9.6 months, respectively.
There were 9 patients with TP53 mutations who underwent hematopoietic stem cell transplant (HSCT), including 8 with de novo AML and 1 with secondary AML. The median relapse-free survival was 16.3 months in patients who underwent HSCT and 4.2 months in patients who did not. The median OS was 16.6 months and 9.8 months, respectively.
Results in the Relapsed/Refractory Cohort
The relapsed/refractory cohort included 18 patients who were previously exposed to venetoclax and 18 who were venetoclax-naïve. Eleven patients in the exposed cohort and 12 in the naive cohort had TP53 mutations.
The median age was 68 (range, 35-79) years in the exposed cohort and 55 (range, 28-71) years in the naïve cohort. The proportion of women was 39% and 44%, respectively. Most patients (89% and 78%) had an ECOG performance status of 1-2, and most (78% and 72%) had adverse cytogenetics.
The CR rate was 19% overall, 0% in the venetoclax-exposed cohort, and 39% in the venetoclax-naïve cohort.
The median follow-up was 17.9 months. The median relapse-free survival was 3.1 months in the exposed cohort and 7.5 months in the naïve cohort. The median OS was 3.1 months and 5.6 months, respectively.
The researchers evaluated safety in all 79 patients. All had at least 1 adverse event (AE), and 90% had at least 1 grade 3 or higher AE. There were no immunologic AEs and no discontinuations due to treatment-related AEs.
The most common treatment-emergent AEs were hypokalemia (61%), hyperbilirubinemia (52%), hypophosphatemia (51%), febrile neutropenia (44%), lung infection (43%), hypocalcemia (41%), diarrhea (41%), and constipation (41%).
The most common grade 3 AEs were febrile neutropenia (44%) and lung infection (35%).
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Daver N, Senapati J, Maiti A, et al. Phase I/II study of azacitidine, venetoclax and magrolimab for newly diagnosed and relapsed/refractory AML. Presented at ASH 2022. December 10-13, 2022. Abstract 61.