Dana FRANGU, Roxana HIRJAN, Bianca CONSTANTIN, Andreea ANDRUNACHE, Mihaela CIRSTEA, Bogdan IONESCU, Camelia STANCIOAICA, Alexandra GHIAUR, Aurelia TATIC
Introduction: FLT3 mutations occur in approximately 30% of acute myeloid leukemia (AML) cases and are associated with high relapse rates and poor prognosis. While second-generation inhibitors like gilteritinib have improved outcomes in the relapsed/refractory (R/R) setting, therapeutic resistance remains a significant challenge. This study evaluates the real-world experience of a single center using an off-label triplet regimen (Azacitidine, Venetoclax and Gilteritinib) as a bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Materials and Methods: We conducted a retrospective, observational study between March 2022 and September 2025. Out of 78 identified FLT3-positive AML patients, 8 patients with R/R disease received the triplet therapy following partial response or disease progression on gilteritinib monotherapy.
Results: Within the subgroup who experienced disease progression under gilteritinib (n = 4 of 8), all patients achieved complete remission (CR) after receiving triple therapy and successfully underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Regarding the safety profile, 63% of patients developed grade 3–4 hematologic toxicities (febrile neutropenia, anemia, thrombocytopenia), while hepatic cytolysis remained mild (grade 1–2), although it was observed in all patients (n = 8). At a median follow-up of 9 months, 75% of patients who underwent allo-HSCT post-triplet therapy remained alive.
Conclusions: Our findings suggest that the triplet combination of azacitidine, venetoclax and gilteritinib is a highly effective salvage strategy. Although careful monitoring is required due to moderate toxicities, particularly hematologic adverse events, it is a viable bridge to transplant for R/R FLT3-mutated AML patients who fail standard monotherapy.
Keywords: relapsed/refractory acute myeloid leukemia, FLT3 mutation, gilteritinib, venetoclax, azacitidine, triple therapy, allogeneic hematopoietic stem cell transplantation
https://doi.org/10.59854/dhrrh.2026.4.2.49
Cite this article
Frangu D., Hirjan R., Constantin B., Andrunache A. et. al, Triple Therapy with Azacitidine, Venetoclax and Gilteritinib as a Therapeutic Option for Adult Patients with Refractory/Relapsed FLT3 Mutated Acute Myeloid Leukemia – A Single Center Experience. DHRRH, 2026, 6(2), https://doi.org/10.59854/dhrrh.2026.4.2.49
