Gilteritinib is approved for the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML) with a FLT3-mutation (FLT3mut+). However, the gilteritinib phase 3 ADMIRAL study (Perl et al NEJM 2019) was conducted prior to widespread adoption of either midostaurin as a component of standard intensive induction and consolidation or post-transplant FLT3 inhibitor maintenance. We performed a retrospective analysis using data from 11 US centers and where we identified 113 patients who received gilteritinib alone or as combination therapy for the treatment of R/R FLT3mut+ AML. The composite CR rate (CRc, defined as CR + CRi + CRp) was 48.7% (n= 55). The CRc rate after treatment with gilteritinib in patients who were treated with only prior 7+3 and midostaurin with or without consolidation was 58% with a median survival of 7.8 months. Survival was longest in patients who obtained a CR, particularly a cMRD (Clinical minimal or measurable residual disease) negative response; this remained significant after censoring at the time of SCT. MAPK pathway activating mutations that are known for gilteritinib resistance (NRAS, KRAS, and PTPN11) had lower CRc (35% vs 60.5%) and lower mOS than patients’ whose leukemia did not express these mutations (4.9 months vs 7.8 months) (HR 2.4- 95% CI 1.1-5.4) p value <0.01.

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