Gain and Loss of FLT3 Mutations in Patients with Acute Myeloid Leukemia: A Noninterventional Cohort Study (CLEVO)

FMS-like tyrosine kinase 3 (FLT3) mutations show variable detectability in relapse/refractory acute myeloid leukemia (AML) with unclear clonal evolution dynamics.

This prospective noninterventional study examined clonal evolution and outcomes from AML diagnosis to relapse/refractory disease occurrences.

Of 650 patients included, 172 were FLT3-positive (FLT3^pos) and 472 were FLT3-negative (FLT3^neg; 99.1% testing rate; unknown FLT3 status, six patients). At first occurrence, the FLT3 testing rate decreased (57.0% [166/291]). Among tested patients, 45 had FLT3^pos and 121 had FLT3^neg AML. A gain or loss of mutations was seen in 15.6% (7/45) of patients with FLT3^pos AML and 14.9% (18/121) of patients with FLT3^neg AML. Median (95% confidence interval [CI]) overall survival was 22.8 (19.6, not estimable [NE]) months across patients (FLT3^pos, NE;FLT3^neg, 20.3 [15.2-23.7] months; hazard ratio [HR] [95% CI] 0.6 [0.5-0.8]). Median (95% CI) disease-free survival across patients was NE (26.3-NE) (FLT3^pos, NE;FLT3^neg, NE; HR [95% CI] 0.8 [0.6-1.1]). Median event-free survival (95% CI) was 11.8 (10.0-15.5) months in all patients (FLT3^pos, 17.2 [11.0-NE] months;FLT3^neg, 10.4 [8.4-13.2] months; HR [95% CI] 0.8 [0.6-1.0]).

Dynamic changes in FLT3 mutation status were observed during these patients' disease course. FLT3^pos status at baseline, but not at first occurrence, was associated with improved outcomes; other confounders should be considered. Timelier FLT3 mutation retesting may aid in personalizing treatment. Graphical abstract available for this article.