Prognostic Impact of FLT3 ‐ ITD Allelic Ratio in AML Patients Treated With High‐Dose Anthracycline and a FLT3 Inhibitor

The prognostic value of FLT3 internal tandem duplication (FLT3-ITD) in acute myeloid leukemia (AML) has traditionally been stratified according to the ITD/wild-type allelic ratio (AR) and NPM1 co-mutation status. We evaluated the prognostic impact of FLT3-ITD AR in 459 newly diagnosed AML patients younger than 60 years enrolled in the prospective BIG-1 study, all treated with high-dose anthracycline-based induction. From 2018 onward, midostaurin was added for FLT3-mutated cases. AR was not associated with composite complete remission (81.7% vs. 79.6% in low vs. high AR, p = 0.85), overall survival (OS) (median 7.6 vs. 6.9 years, p = 0.25), relapse-free survival (median 2.0 vs. 1.7 years, p = 0.50), or event-free survival (median 1.4 vs. 1.2 years, p = 0.58). In multivariable analyses, only midostaurin exposure (adjusted hazard ratio [aHR] 0.69, 95% CI 0.50-0.95, p = 0.024) and adverse ELN-2022 risk (aHR 1.66, 95% CI 1.18-2.34, p = 0.004) were independently associated with OS. Allogeneic hematopoietic stem cell transplantation was associated with improved relapse-free (aHR 0.40, 95% CI 0.29-0.55, p < 0.001) and event-free survival (aHR 0.37, 95% CI 0.27-0.51, p < 0.001), but not OS. These results indicate that FLT3-ITD AR has no independent prognostic impact in younger AML patients treated with intensive anthracycline-based chemotherapy and midostaurin in contemporary clinical practice.