Mónica Alejandra Romero Riquelme, Gaspar Aspas Requena, Pilar Lloret-Madrid, Cristina Gil, Eliana Aguiar, Mar Tormo, Teresa Del Bernal Del Castillo, Eduardo Rodríguez Arbolí, Josefina Serrano, Joaquín Sánchez-García, Carlos Rodríguez-Medina, José Mário Mariz, Rosa Ayala, Joaquín Martínez-López, María Luz Amigo, Susana Vives, Lorenzo Algarra Algarra, Raimundo García Boyero, Joana Brioso, Tamara Castaño, Juan M Bergua Burgués, Olga Salamero, María Francisca Bass Maturana, Mercedes Colorado, María García Fortes, María José Sayas Lloris, Belén Vidriales Vicente, Carmen Chillón, Esther Pérez Santaolalla, María Dolores Madrigal, Jorge Labrador Gómez, María José García Pérez, Soledad Casado Calderón, Manuel Pérez Encinas, Amaia Balerdi Malcorra, María Solé Rodríguez, Lara María Gómez García, Pilar Herrera Puente, Olga Arce Fernández, Manuel Barrios García, Víctor Noriega, Rosa Fernández, Mamen Mateos, Carolina Lacalzada, Ágata Almela Gallego, María Carmen García Garay, Carmen Couto, José Antonio Pérez-Simón, Eva Barragán González, Pau Montesinos
Mutations in FLT3 are present in approximately 30% of patients with AML. The addition of midostaurin (MIDO) to intensive chemotherapy (IC) became standard of care following the RATIFY trial, but comprehensive real-world data spanning the full adult age spectrum and including both FLT3-ITD and FLT3-TKD mutations remain limited. We retrospectively analyzed 1658 adults aged 14-85 years with newly diagnosed FLT3-mutated AML from 129 PETHEMA registry centers: 469 received IC + MIDO and 1189 IC alone. Composite complete remission was higher with IC + MIDO than IC (81.4% vs. 71.7%; p < 0.001) and Day 30 mortality was substantially lower (2.1% vs. 7.1%; p < 0.001). Median overall survival was 47.2 versus 19.3 months (HR 0.64; 95% CI, 0.53-0.76; p < 0.001), and the benefit was sustained after multivariable adjustment (HR 0.73; p = 0.017). In 261 propensity score-matched pairs, the effect was attenuated, remaining significant for event-free survival (HR 0.77; p = 0.029) and showing a nonsignificant trend for OS (HR 0.77; p = 0.06). Allogeneic hematopoietic stem cell transplantation in first remission was more frequent in the IC + MIDO cohort (48.9% vs. 41.3%; p = 0.023). Time-dependent analyses showed the largest MIDO effect among autologous and non-transplanted patients (OS HR 0.45; p = 0.138, and HR 0.69; p = 0.014, respectively). The benefit of MIDO was consistent irrespective of FLT3 mutation type, FLT3-ITD allelic burden, cytogenetic risk, and gender, while less improvement occurred among NPM1 wild type and secondary AML patients. This large real-world cohort confirms the survival benefit of MIDO plus IC across the full adult age spectrum, supporting its standard-of-care status in FLT3-mutated AML.