The impact of <i>FLT3</i> mutation clearance and treatment response after gilteritinib therapy on overall survival in patients with <i>FLT3</i> mutation–positive relapsed/refractory acute myeloid leukemia

Abstract

Abstract The FLT3 inhibitor gilteritinib has clinical activity in patients with FLT3 ‐mutated ( FLT3 mut+ ) relapsed/refractory (R/R) acute myeloid leukemia (AML). The impact of FLT3 mutation clearance and the achievement of composite complete remission (CRc) and complete remission/complete remission with partial hematologic recovery (CR/CRh) on overall survival (OS) in patients with FLT3 mut+ R/R AML treated with single‐agent gilteritinib in a phase 1/2 trial were evaluated. Using next‐generation sequencing, a FLT3 ‐ITD variant allele frequency of ≤10 −4 was used to define FLT3 ‐ITD clearance in patients with no morphologic leukemia (ie, CRc). A total of 108 patients with FLT3 ‐ITD‐positive ( FLT3 ‐ITD+) R/R AML were analyzed; 95 of these patients had received ≥80‐mg/day gilteritinib. Ten of the 95 patients had FLT3 ‐ITD clearance; eight of these 10 patients achieved CRc and were considered negative for measurable residual disease. There was a trend toward longer OS in patients who attained CRc with FLT3 ‐ITD clearance (131.4 weeks) versus those who achieved CRc and did not have FLT3 ‐ITD clearance ( n = 41; 43.3 weeks; HR = 0.416; p = 0.066). Among patients treated with ≥80‐mg/day gilteritinib who achieved CR/CRh ( n = 24), seven had FLT3 ‐ITD clearance. Among patients who received 120‐mg/day gilteritinib, those who achieved CR/CRh had a longer median OS (70.6 weeks) and higher 52‐week survival probability (66.7%) than patients who did not achieve CR/CRh ( n = 71; median OS, 41.7 weeks; 52‐week survival probability, 20.2%). Overall, these data suggest that gilteritinib can induce deep molecular responses in patients with FLT3 ‐ITD+ R/R AML, and in the setting of CRc or CR/CRh, these responses may be associated with prolonged survival.

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