Abstract / Summary
Background: Mutations of the FLT3 gene, particularly internal tandem duplication (FLT3-ITD), define a biologically aggressive AML subtype with historically poor outcomes. Here we retrospectively assessed the clinical performance and tolerability of sorafenib with venetoclax plus azacitidine (VA) as front-line therapy in patients with newly diagnosed FLT3-ITD-mutated AML. Methods: Forty-five consecutive patients who received sorafenib plus VA induction were retrospectively analyzed. Post-remission therapy comprised sorafenib-based chemotherapy consolidation, continued sorafenib-VA, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) after consolidation therapy according to clinical indication and guidelines. Composite complete remission (CRc), measurable residual disease (MRD), overall survival (OS), and relapse-free survival (RFS) were assessed. Results: The CR/CRi rate was 95.6% (43/45), and the FCM-MRD negativity rate after induction was 90.7%. At a median follow-up of 20.3 months, the 2-year OS and RFS of the entire cohort were 65.3% and 57.3%, respectively. The relapse rate in the patients receiving post-remission allo-HSCT after consolidation therapy was lower. Continued sorafenib-VA achieved a 2-year OS of 57.1% and a 2-year RFS of 64%. Multivariable analysis identified chemotherapy-based post-remission therapy (p = 0.016) and detectable MRD after the second consolidation cycle (p = 0.004) as independent adverse prognostic factors for RFS. No treatment-related mortality occurred. Conclusions: Sorafenib plus VA is a cost-effective, tolerable induction regimen achieving high remission and MRD negativity rates in FLT3-ITD-mutant AML. For transplant-eligible patients, allo-HSCT significantly improves long-term survival; for transplant-ineligible patients, continued sorafenib-VA yields sustained benefit.