A triplet therapy consisting of lower-intensity chemotherapy, specifically monotherapy with a hypomethylating agent (HMA), combined with an FLT3 inhibitor and venetoclax may be an effective frontline regimen for older or unfit patients with FLT3-mutated acute myeloid leukemia (AML), according to a retrospective analysis.
The results were published in Blood Cancer Journal in a paper by Musa Yilmaz, MD, of The University of Texas MD Anderson Cancer Center, and colleagues.
The study included 87 newly diagnosed patients with FLT3-mutated AML treated on the triplet (n=27) and doublet lower-intensity chemotherapy plus FLT3 inhibitor (n=60) regimens.
Triplet therapy was associated with significantly higher rates of complete remission (CR; 67% vs 32%; P=.002), CR/CR with incomplete hematologic recovery (93% vs 70%, P=.02), FLT3-polymerase chain reaction negativity (96% vs 54%; P<.01), and flow cytometry negativity (83% vs 38%; P<.01) compared with doublets.
At the end of the first cycle, the median time to absolute neutrophil count >0.5 (40 vs 21 days; P=.15) and platelet >50,000 (29 vs 25 days; P=.6) among responders was numerically longer with triplets, but 60-day mortality was similar (7% vs 10%). With a median follow-up of 24 months (median, 12 months for triplet arm and 63 months for doublet arm), patients receiving a triplet regimen had a longer median overall survival (not reached vs 9.5 months; P<.01).
“[Lower-intensity chemotherapy] combined with [an] FLT3 inhibitor and venetoclax (triplet) may be an effective frontline regimen for older/unfit FLT3-mutated AML that should be further validated prospectively,” the authors concluded.
Yilmaz M, Kantarjian H, Short NJ, et al. Hypomethylating agent and venetoclax with FLT3 inhibitor “triplet” therapy in older/unfit patients with FLT3 mutated AML. Blood Cancer J. 2022;12(5):77. doi:10.1038/s41408-022-00670-0