Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study



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Ayala Díaz, Rosa María and Carreño Tarragona, Gonzalo and Barragán, Eva and Boluda, Blanca and Larráyoz, María J. and Chillón, María Carmen and Carrillo Cruz, Estrella and Bilbao, Cristina and Sánchez García, Joaquín and Bernal, Teresa and Martínez Cuadrón, David and Gil, Cristina and Serrano, Josefina and Rodríguez Medina, Carlos and Bergua, Juan and Pérez Simón, José A. and Calbacho, María and Alonso Domínguez, Juan Manuel and Labrador, Jorge and Tormo, Mar and Amigo, Maria Luz and Herrera Puente, Pilar and Rapado, Inmaculada and Sargas, Claudia and Vázquez, Iria and Calasanz, María J. and Gómez Casares, Teresa and García Sanz, Ramón and Sanz, Miguel A. and Martínez López, Joaquín and Montesinos, Pau (2022) Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study. Cancers, 14 (23). p. 5799. ISSN 2072-6694

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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.

Item Type:Article
Uncontrolled Keywords:FLT3–ITD mutation and ratio; Real-world outcomes; Acute myeloid leukemia (AML); Prognosis; Outcome; Death; Relapse; Survival
Subjects:Medical sciences > Medicine
Medical sciences > Medicine > Oncology
ID Code:78383
Deposited On:19 May 2023 09:54
Last Modified:19 May 2023 09:54

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