Triplet therapy for FLT3-mutated acute myeloid leukemia in Puerto Rico: A retrospective study.

Abstract

e18534 Background: Acute myeloid leukemia (AML) is a highly heterogeneous disease frequently driven by mutations in the FMS-like tyrosine kinase 3 (FLT3) gene, which occurs in approximately 30% of AML patients. Current treatment options for FLT3-mutated AML are suboptimal, particularly in older or unfit patients, with limited efficacy using standard regimens like venetoclax and azacitidine. A recent publication by N. Short and the MD Anderson group revealed a favorable response to the triple therapy in FLT3 AML. Our study investigates the efficacy of a novel triplet regimen combining venetoclax, azacitidine, and gilteritinib (an FLT3 inhibitor) in the Puerto Rican population with FLT3-mutated AML. Methods: We conducted a retrospective analysis of AML patients treated at San Juan City Hospital. Patient demographics, bone marrow biopsy results, cytogenetic, and molecular data were collected from electronic medical records. The study received institutional review board approval, adhering to the principles of the Declaration of Helsinki. Results: Among the 193 diagnosed AML patients identified during the study period (2020-2024), 21% (N = 40) exhibited FLT3 mutations. Within this subset, eight patients with FLT3-mutated AML (median age: 63 years old; gender distribution: 5 males, 3 females), received the triplet therapy. Four subjects were treated in the frontline setting, and the other four in the relapsed/refractory setting. Seventy-five percent (3/4) of patients achieved complete cytogenetic and molecular response (CR) in the frontline setting, with 2 proceeding to allogeneic stem cell transplant. All patients in this group remain alive. In terms of the Relapsed/Refractory setting, 50% (2/4) achieved CR and proceeded to stem cell transplant. The remaining two patients experienced refractory disease with infectious complications and succumbed to their illness. Conclusions: This study is the first to describe FLT3 mutated AML patients from Puerto Rico treated with the triplet therapy. The obtained results demonstrated a promising high response rate in the frontline setting for older or unfit patients with FLT3-mutated AML, with a significant portion achieving durable remission. These findings underscore the potential of venetoclax, azacitidine, and gilteritinib as a new therapeutic option for this population, warranting further research to establish this regimen as a standard of care.