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

Jessica K. Altman*, Alexander E. Perl, Jason E. Hill, Matt Rosales, Erkut Bahceci, Mark J. Levis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalCancer medicine
DOIs
StateAccepted/In press - 2020

Keywords

  • FLT3 inhibitor
  • Fms-like tyrosine kinase 3
  • internal tandem duplication
  • morphologic remission

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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