The impact of FLT3 mutation clearance and treatment response after gilteritinib therapy on overall survival in patients with FLT3 mutation-positive relapsed/refractory acute myeloid leukemia.
The FLT3 inhibitor gilteritinib has clinical activity in patients with FLT3-mutated (FLT3mut+ ) 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 FLT3mut+ 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.
['Altman|Jessica K|JK|', 'Perl|Alexander E|AE|', 'Hill|Jason E|JE|', 'Rosales|Matt|M|', 'Bahceci|Erkut|E|', 'Levis|Mark J|MJ|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000814:Aniline Compounds D019008:Drug Resistance, Neoplasm D005260:Female D005500:Follow-Up Studies D006801:Humans D015470:Leukemia, Myeloid, Acute D008297:Male D008875:Middle Aged D009154:Mutation D011379:Prognosis D047428:Protein Kinase Inhibitors D011719:Pyrazines D015996:Survival Rate D055815:Young Adult D051941:fms-Like Tyrosine Kinase 3
FLT3 inhibitor Fms-like tyrosine kinase 3 internal tandem duplication morphologic remission