1. 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.
- Author
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Ofran, Yishai, Leiba, Ronit, Frisch, Avraham, Horesh, Nurit, Henig, Israel, Yehudai‐Ofir, Dana, Moshe, Yakir, Neaman, Miriam, Ganzel, Chezi, Gal‐Rabinovich, Kinneret, Hellmann, Ilana, Weinstein, Vladimir, Berger, Tamar, and Wolach, Ofir
- Subjects
ACUTE myeloid leukemia ,STEM cell transplantation ,COMBINATION drug therapy - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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