Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/16136
Impact of FLT3-ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study.
Ayala, Rosa | Carreño-Tarragona, Gonzalo CNIC | Barragán, Eva | Boluda, Blanca | Larráyoz, María J | Chillón, María Carmen | Carrillo-Cruz, Estrella | Bilbao, Cristina | Sánchez-García, Joaquín | Bernal, Teresa | Martinez-Cuadron, David | Gil, Cristina | Serrano, Josefina | Rodriguez-Medina, Carlos | Bergua, Juan | Pérez-Simón, José A | Calbacho, María | Alonso-Domínguez, Juan M | Labrador, Jorge | Tormo, Mar | Amigo, Maria Luz | Herrera-Puente, Pilar | Rapado, Inmaculada | Sargas, Claudia | Vazquez, Iria | Calasanz, María J | Gomez-Casares, Teresa | García-Sanz, Ramón | Sanz, Miguel A | Martinez-Lopez, Joaquin CNIO | Montesinos, Pau
Cancers (Basel). 2022;14(23):5799.
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.
FLT3-ITD mutation and ratio | real-world outcomes | ACUTE MYELOID LEUKEMIA | PROGNOSIS | OUTCOME | DEATH | RELAPSE | SURVIVAL
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