Intensive Chemotherapy with or without Midostaurin in Adults ≥60 years 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 (≥ 60 years) 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 ≥ 60 years (median age 67.5 years; 35.6% ≥70 years).After a median follow-up of 46.0 months, 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). Median overall survival (OS) was 24.2 months for MIDO + IC versus 8.6 months 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 4.6 months; 5-year EFS: 36.0% vs 10.1%) and relapse-free survival (RFS; median 20.2 vs 8.0 months; 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 multivariable 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 (n = 236).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.