Gilteritinib Clinical Activity in Relapsed/Refractory FLT3 Mutated AML Previously Treated with FLT3 inhibitors. American journal of hematology Numan, Y., Abdel Rahman, Z., Grenet, J., Boisclair, S., Bewersdorf, J. P., Collins, C., Barth, D., Fraga, M., Bixby, D. L., Zeidan, A. M., Yilmaz, M., Desai, P., Mannis, G., Deutsch, Y. E., Abaza, Y., Dinner, S., Frankfurt, O., Litzow, M., Al-Kali, A., Foran, J. M., Sproat, L. Z., Jovanovic, B., Daver, N., Perl, A. E., Altman, J. K. 2022


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. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ajh.26447

View details for PubMedID 34981560