Hypomethylating Agent, Venetoclax, and Gilteritinib Triplet Regimen for R/R FLT3-Mutated AML

Combining a hypomethylating agent, venetoclax, and gilteritinib (HMA-VEN-GILT) as a triplet regimen yielded beneficial outcomes among patients with relapsed/refractory (R/R) fms‐like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), according to findings from a study published in Leukemia & Lymphoma. This regimen may be used as a bridge to allogeneic stem cell transplantation (ASCT) for these patients. 

Dat Ngo, MD, City of Hope, Duarte, California, and coauthors stated that R/R FLT3-mutated AML “remains a difficult and hard to treat entity.” Prior research indicates that gilteritinib, an FLT3 inhibitor, can improve overall survival outcomes among patients with R/R AML. The study authors aimed to expand the current research on combining gilteritinib with other agents by assessing a triplet regimen consisting of a hypomethylating agent, venetoclax, and gilteritinib. 

A total of 22 patients with R/R FLT3-mutated AML were enrolled in this study and administered HMA-VEN-GILT. Results indicated that the combination yielded an overall response rate of 77.3% (n = 17), a complete remission of 4.5% (n = 1), a complete remission with an incomplete recovery count of 13.6% (n = 3), and a morphologic leukemia-free state of 59.1% (n = 13). 

Among the 17 responding patients, the relapse rate at the median follow-up of 10.4 months was 29.4% (n = 5), the median time to relapse was 69 days (ranging from 35 to 298 days), the 6-month overall survival was 84%, and the median overall survival was 10.1 months. The study authors noted that 36.4% (n = 8) of the total patients enrolled continued to hematopoietic stem cell transplantation. 

“HMA-VEN-GILT for the treatment of R/R FLT3 AML is feasible and can be used as a bridge to allogeneic transplantation,” concluded Ngo and the coauthors. 

Source: 

Ngo D, Tinajero J, Li S, et al. Treatment of relapsed or refractory FLT-3 acute myelogenous leukemia with a triplet regimen of hypomethylating agent, venetoclax, and gilteritinib. Leuk & Lymph. Published online: January 2, 2024. doi: 10.1080/10428194.2023.2292473