Intensive Chemotherapy With or Without Midostaurin in Adults ?60Years Old With FLT3-Mutated AML: A FILO-DATAML-PETHEMA Real-World Study.

Abstract

The addition of midostaurin (MIDO) to intensive chemotherapy (IC) improves survival in younger adults with FLT3-mutated acute myeloid leukemia (AML); however, real-world data in elderly patients (?60years) are limited. This large, retrospective, multicenter study from three European registries (PETHEMA, FILO, DATAML) evaluated MIDO+IC (n=194) versus IC alone (n=371) in 565 patients with FLT3-mutated AML aged ?60years (median age 67.5years; 35.6% ?70years). MIDO+IC was associated with lower day-60 early death (8.2% vs. 21.4%, p<0.0001) and higher composite complete remission (CRc) rates (78.9% vs. 63.1%, p<0.0001). After a median follow-up of 46.0months, median overall survival (OS) was 24.2months for MIDO+IC versus 8.7months for IC (p<0.0001), with 5-year OS rates of 40.6% vs. 12.9%, respectively. Event-free survival (EFS; median 13.5 vs. 4.6months; 5-year EFS: 36.0% vs. 10.1%) and relapse-free survival (RFS; median 20.2 vs. 8.0months; 5-year RFS: 45.4% vs. 15.7%) were also significantly improved (both p<0.0001). The 5-year cumulative incidence of relapse was lower with MIDO+IC (47.8% vs. 67.1%, p<0.001). In multivariate analyses, midostaurin was an independent favorable prognostic factor for CRc (aOR 1.97 [95% CI: 1.29-2.98]), OS (aHR 0.46 [95% CI: 0.36-0.58]), EFS (aHR 0.49 [95% CI: 0.39-0.60]), and RFS (aHR 0.47 [CI: 0.36-0.62]) (all p?0.002). These benefits were confirmed by propensity score matching. This large real-world study demonstrates that combining midostaurin with IC significantly improves remission rates and survival outcomes in elderly patients with FLT3-mutated AML, supporting its consideration in this population.