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Gilteritinib monotherapy for relapsed/refractory FLT3 mutated acute myeloid leukemia: a real-world, multi-center, matched analysis

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Abstract

Patients with FLT3-mutated relapsed or refractory (R/R) acute myeloid leukemia (AML) have a dismal prognosis. Gilteritinib is a FLT3 tyrosine kinase inhibitor (TKI) recently approved for patients with R/R AML. We aimed to characterize real-world data regarding gilteritinib treatment in FLT3-mutated R/R AML and to compare outcomes with matched FLT3-mutated R/R AML patients treated with chemotherapy-based salvage regimens. Twenty-five patients from six academic centers were treated with gilteritinib for FLT3-mutated R/R AML. Eighty percent were treated with a prior intensive induction regimen and 40% of them received prior TKI therapy. Twelve patients (48%) achieved complete response (CR) with gilteritinib. The estimated median overall survival (OS) of the entire cohort was eight (CI 95% 0–16.2) months and was significantly higher in patients who achieved CR compared to those who did not (16.3 months, CI 95% 0–36.2 vs. 2.6 months, CI 95% 1.47–3.7; p value = 0.046). In a multivariate cox regression analysis, achievement of CR was the only predictor for longer OS (HR 0.33 95% CI 0.11–0.97, p = 0.044). Prior TKI exposure did not affect OS but was associated with better event-free survival (HR 0.15 95% CI 0.03–0.71, p = 0.016). An age and ELN-risk matched comparison between patients treated with gilteritinib and intensive salvage revealed similar response rates (50% in both groups); median OS was 9.6 months (CI 95% 2.3–16.8) vs. 7 months (CI 95% 5.1–8.9) in gilteritinib and matched controls, respectively (p = 0.869). In conclusion, in the real-world setting, gilteritinib is effective, including in heavily pre-treated, TKI exposed patients.

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Authors and Affiliations

  1. Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel

    Shai Shimony, Eitan Kugler, Moshe Yeshurun, Pia Raanani & Ofir wolach

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Shai Shimony, Eitan Kugler, Ron Ram, Yakir Moshe, Moshe Yeshurun, Pia Raanani & Ofir wolach

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Shai Shimony

  4. Hematology Division, Faculty of Medicine, Chaim Sheba Medical Center, Tel Aviv University, Tel Hashomer, Israel

    Jonathan Canaani

  5. Department of Hematology, Hadassah Medical Center, Hebrew University Faculty, Jerusalem, Israel

    Boaz Nachmias, Vladimir Vainstein & Shlomzion Aumann

  6. BMT Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Ron Ram & Yakir Moshe

  7. Department of Hematology and Bone Marrow Transplantation, Rappaport Faculty of Medicine - Technion, Rambam Health Care Campus, Haifa, Israel

    Israel Henig & Avraham Frisch

  8. Department of Hematology, Shaare Zedek Medical Center, Hebrew University Faculty, Jerusalem, Israel

    Chezi Ganzel & Yishai Ofran

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  1. Shai Shimony
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The original version of this article was revised: This article was originally published with a missing author (Dr. Israel Henig).

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Shimony, S., Canaani, J., Kugler, E. et al. Gilteritinib monotherapy for relapsed/refractory FLT3 mutated acute myeloid leukemia: a real-world, multi-center, matched analysis. Ann Hematol 101, 2001–2010 (2022). https://doi.org/10.1007/s00277-022-04895-8

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