Regional practice differences significantly affect the benefit of post-HCT gilteritinib in FLT3-ITD AML

BMT CTN 1506 (MORPHO) was a phase 3 study of post-hematopoietic cell transplantation (HCT) maintenance with gilteritinib vs placebo for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) in first remission. Subgroup analysis indicated a significant benefit of post-HCT gilteritinib for participants in North America but no benefit for those in Europe or Asia. We conducted a post hoc analysis of the data focusing on the time from AML diagnosis to HCT, pre-HCT FLT3 inhibitor use, and FLT3-ITD measurable residual disease (MRD). Participants who underwent transplantation <120 days from AML diagnosis and/or those treated with FLT3 inhibition before HCT were more likely to have improved survival from post-HCT gilteritinib. Pre-HCT MRD levels were higher (P = .001) in participants who underwent transplantation within 120 days from diagnosis and in those treated with an FLT3 inhibitor before HCT and underwent transplantation within 120 days (P = .008). Pre-HCT MRD was dependent on both FLT3 inhibitor use and time to HCT, because participants treated with successive courses of chemotherapy + FLT3 inhibition had successively lower MRD by the time of HCT. Time from AML diagnosis to HCT and pre-HCT FLT3 inhibitor use both appeared to affect MRD levels immediately before HCT, and geographic differences in these 2 practice patterns likely accounted for the observed regional differences in benefit from post-HCT gilteritinib. Increasing the number of courses of treatment before HCT may lower MRD sufficiently to eliminate the need for post-HCT inhibition, but with a presumed risk of some patients experiencing early progression. This trial was registered at www.clinicaltrials.gov as #NCT02997202.