Midostaurin in combination with chemotherapy is most effective in patients with acute myeloid leukemia presenting with high FLT3-ITD allelic ratio who proceed to allogeneic stem cell transplantation while in first complete remission

Yishai Ofran, Ronit Leiba, Avraham Frisch, Nurit Horesh, Israel Henig, Dana Yehudai-Ofir, Yakir Moshe, Miriam Neaman, Chezi Ganzel, Kinneret Gal-Rabinovich, Ilana Hellmann, Vladimir Weinstein, Tamar Berger, Ofir Wolach

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Midostaurin, a multikinase and FLT3 inhibitor, is the first non-chemotherapy agent approved and widely adopted for the treatment of FLT3-ITD acute myeloid leukemia (AML). Yet, its role in improving survival of patients referred to allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1) needs to be defined. Methods: This multicenter study retrospectively evaluated the outcome of 119 FLT3-ITD AML patients [59 (49.6%) males and 60 females] intensively treated between 2015 and 2019 at five Israeli centers. In our cohort, allo-SCT in CR1 was widely implemented (47%) and patient stratification was based on the current allelic ratio (AR) cutoff of 0.5. Results: Ninety-eight patients (82.3%) achieved CR1/CR with incomplete count recovery (CRi). Death during induction was reported in 7 (5.9%) patients. In multivariate analysis, midostaurin use and allo-SCT in CR1 were the most significant factors affecting overall survival (OS). Midostaurin incorporation in chemotherapy regimens significantly improved CR + CRi rates (P =.002), reduced relapse rates (P =.02), and was remarkably advantageous for high-AR patients (2-year OS 82%). In low-AR patients, the midostaurin effect was much less prominent. Conclusions: Our results demonstrate benefits of midostaurin incorporation in intensive chemotherapy regimens, particularly for high-AR AML patients to whom it should be offered along with allo-SCT in CR1.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalEuropean Journal of Haematology
Volume106
Issue number1
DOIs
StatePublished - Jan 2021
Externally publishedYes

Keywords

  • acute myeloid leukemia
  • allogeneic stem cell transplantation
  • fms-like tyrosine kinase 3-internal tandem duplication
  • midostaurin

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