Gilteritinib + azacitidine + venetoclax in ND FLT3m AML: Phase II trial results

Long-term results from a prospective, single-center phase II trial (NCT04140487) evaluating gilteritinib + azacitidine + venetoclax in 30 patients with newly diagnosed (ND) FLT3-mutated (FLT3m) acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy (IC) were published in Blood Advances by Short et al. The primary endpoint was the composite complete remission (CRc) rate within 2 cycles of therapy.

Key data: The CRc rate was 96%, with complete remission (CR) in 90% and CR with incomplete hematologic recovery (CRi) in 6% of patients. At a median follow-up of 41.5 months, the median relapse-free survival (RFS) and overall survival (OS) were 23.4 and 29.7 months, respectively; 3-year RFS and OS rates were 43% and 46%, respectively. In 67% of evaluable relapses, the FLT3 mutation was no longer detectable. Survival outcomes were similar regardless of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first remission. Baseline RAS pathway mutations were associated with numerically worse survival outcomes vs those without. The most common Grade ≥3 non-hematologic adverse events (AEs) were infection (63%), febrile neutropenia (40%), and sepsis (17%).

Key learning: Gilteritinib + azacitidine + venetoclax was associated with durable remissions and encouraging long-term survival in adults with ND FLT3m AML who were ineligible for IC, supporting prospective randomized evaluation of this triplet regimen.