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Midostaurin in combination with intensive chemotherapy is safe and associated with improved remission rates and higher transplantation rates in first remission—a multi-center historical control study

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Abstract

The addition of midostaurin, a FLT3-inhibitor, to intensive chemotherapy (IC) was previously shown to improve outcome of younger patients with FLT3-mutated AML. The toxicity and efficacy of adding midostaurin to IC in patients not originally included in the RATIFY study or with intensified daunorubicin dosing are unknown. We conducted a retrospective, multi-center, historical-control study to characterize the safety and efficacy of adding midostaurin to IC in a “real-world” setting. Sixty-nine adult patients were included in the analysis (midostaurin n = 34, historical controls n = 35) with a mean follow-up of 18.4 (± 15) months. Median age of patients was 60 (range 26–82) years; 32% and 20% of patients were > 65 and 70 years, respectively. No differences in baseline characteristics were noted between the groups. Midostaurin was administered with 90 mg/m2 daunorubicin in 29% of patients; One-third of patients experienced dose reductions/interruptions during midostaurin therapy. Overall toxicity was comparable between the midostaurin and control groups.CR/CRi rates were higher in patients treated with midostaurin compared with controls (80% vs. 57%, p = 0.047) and significantly more patients in the midostaurin group were transplanted in first remission (95% vs. 68%, p = 0.04).Median OS and DFS were higher in the midostaurin vs. control group (not reached vs. 11 months (p = 0.085) and 13 vs. 6 months (p = 0.09), respectively). In our analysis, midostaurin was not associated with increased toxicity including in older patients, in those with secondary AML or when administered with intensified daunorubicin dosage. Higher remission rates in the midostaurin group and increased transplantation rates in first CR were associated with a trend towards better outcomes.

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Authors and Affiliations

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

    Tamar Berger, Uri Rozovski, Moshe Yeshurun, Pia Raanani & Ofir Wolach

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

    Tamar Berger, Uri Rozovski, Yakir Moshe, Ilana Hellmann, Adina Aviram, Maya Koren-Michowitz, Moshe Yeshurun, Ron Ram, Pia Raanani & Ofir Wolach

  3. Bone Marrow Transplantation Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

    Yakir Moshe & Ron Ram

  4. Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel

    Shilo Yaari, Avraham Frisch & Yishai Ofran

  5. The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel

    Shilo Yaari, Avraham Frisch & Yishai Ofran

  6. Department of Hematology, Meir Medical Center, Kfar Saba, Israel

    Ilana Hellmann

  7. Department of Hematology, Shamir Medical Center, Zeriffin, Israel

    Arie Apel & Maya Koren-Michowitz

  8. Hematological Laboratories, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel

    Adina Aviram

Authors
  1. Tamar Berger
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  2. Uri Rozovski
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  3. Yakir Moshe
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  10. Moshe Yeshurun
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  11. Ron Ram
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  14. Ofir Wolach
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Corresponding author

Correspondence to Ofir Wolach.

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Conflict of interest

OW, YO, and PR report past membership on an advisory board for Novartis, OW received speaker honoraria from Novartis.

Midostaurin was supplied by Novartis via an extended access program from April 2016 to January 2018.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Berger, T., Rozovski, U., Moshe, Y. et al. Midostaurin in combination with intensive chemotherapy is safe and associated with improved remission rates and higher transplantation rates in first remission—a multi-center historical control study. Ann Hematol 98, 2711–2717 (2019). https://doi.org/10.1007/s00277-019-03795-8

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  • DOI: https://doi.org/10.1007/s00277-019-03795-8

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