Timing of response in patients with relapsed/refractory FLT3 ^mut+ acute myeloid leukemia treated with gilteritinib

This post hoc pooled analysis of ADMIRAL and COMMODORE trials aimed to determine if response kinetics differ for gilteritinib monotherapy in relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML). In total, 205 patients achieved composite complete remission (CRc). This analysis only included the 166 patients (81.0%) who achieved CRc before on-study hematopoietic stem cell transplantation (HSCT). Of these, 148 patients (89.2%) achieved CRc within 6 gilteritinib cycles, 60 patients (36.1%) after cycle 2, and 119 patients (71.7%) after cycle 4. We defined early responders (ERs; n = 60) and later responders (LRs; n = 106) as those who achieved CRc within 2 cycles and after cycle 3, respectively. Multivariate logistic regression analysis indicated that female patients and patients with nucleophosmin 1 comutations were more likely to be ERs than LRs. Median CRc duration was 2.7 months (range, 0-66) for ERs and 3.5 months (range, 0-61) for LRs. More LRs (41 of 106 patients [38.7%]) had best response of CR vs ERs (13 of 60 patients [21.7%]). Median overall survival indexed at CRc date was 9 months for ERs and 10 months for LRs. In ERs and LRs, 14 of 60 patients (23.3%) and 20 of 106 patients (18.9%) underwent HSCT respectively. The rate of drug-related grade ≥3 adverse events was 11.4 events per patient-years in ERs and 7.8 events per patient-years in LRs. Patients with R/R FLT3-mutated AML should continue gilteritinib monotherapy, if tolerated, for a minimum of 6 cycles because later responses can occur. These trials were registered at www.clinicaltrials.gov as NCT02421939 (ADMIRAL) and NCT03182244 (COMMODORE).