Impact of FLT3-ITD mutation status and its ratio in a cohort of 2901 patients undergoing upfront intensive chemotherapy: a PETHEMA registry study

FLT3-ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of F...

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Detalles Bibliográficos
Autores: Ayala, Rosa, Carreño-Tarragona, Gonzalo, Barragán, Eva, Boluda, Blanca, Larráyoz, María José, Chillón, María Carmen, Carrillo-Cruz, Estrella, Bilbao, Cristina, Sánchez-García, Joaquín, Bernal del Castillo, Teresa, Martínez-Cuadrón, David, Gil, Cristina, Serrano, Josefina, Rodríguez-Medina, Carlos, Bergua, Juan, Pérez-Simón, José A., Calbacho, María, Alonso-Domínguez, Juan M., Labrador, Jorge, Tormo, Mar, Amigo, María Luz, Herrera-Puente, Pilar, Rapado, Inmaculada, Sargas, Claudia, Vázquez Urio, Iria, Calasanz, María José, Gómez-Casares, Teresa, García-Sanz, Ramón, Sanz, Miguel A., Martínez-López, Joaquín, Montesinos, Pau
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad Pública de Navarra
Repositorio:Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
OAI Identifier:oai:academica-e.unavarra.es:2454/52480
Acceso en línea:https://hdl.handle.net/2454/52480
Access Level:acceso abierto
Palabra clave:Acute myeloid leukemia (AML)
Death
FLT3-ITD mutation and ratio
Outcome
Prognosis
Real-world outcomes
Relapse
Survival
Descripción
Sumario:FLT3-ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3-ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3-ITD mutations. In multivariate analyses, patients with an FLT3-ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3-ITD-mutated patients, median OS gradually decreased according to FLT3-ITD status and ratio (34.3 months FLT3-ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months ≥ 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3-ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3-ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3-ITD status in all patients, and we found that the group of FLT3-ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3-ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3-ITD mutations.

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