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Venetoclax in patients with acute myeloid leukemia refractory to hypomethylating agents—a multicenter historical prospective study

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Abstract

Patients with acute myeloid leukemia (AML) who progress after exposure to hypomethylating agents (HMA) have a dismal prognosis. We hypothesized that the addition of venetoclax, a BCL-2 inhibitor, to AML patients who previously failed HMA might overcome resistance. Adult patients (≥ 18 years) with AML were eligible if leukemia relapsed after, or was refractory to HMA. In general, in addition to venetoclax, patients continued HMA or other low-intensity therapies. Patients who previously underwent allogeneic hematopoietic cell transplantation (HCT) were also eligible. Data were analyzed in November 2018. Twenty-three patients were treated between October 2016 and October 2018 and were eligible for this study. Median age was 76 years and 6 patients had leukemia that relapsed post allogeneic HCT. None of the patients experienced tumor lysis syndrome and toxicities were as expected and manageable. Febrile neutropenia was the most common toxicity (78% of patients). Median hospitalization time was 13 days. Forty-three percent of the patients achieved CR/CRi. Overall survival (OS) was 74% at 6 months and median OS in patients who achieved remission was 10.8 months. Higher number of blasts in both bone marrow and peripheral blood was associated with lower chances of CR, while higher WBC, LDH, and bone marrow or peripheral blasts were associated with increased mortality rate. The addition of venetoclax to patients with HMA-refractory AML may result in a substantial anti-leukemic activity, specifically in those achieving complete remission. This should be further tested in a well-designed prospective trial.

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Authors and Affiliations

  1. BMT Unit, Tel Aviv Medical Center, 6 Weizman St., Tel Aviv, Israel

    Ron Ram, Odelia Amit, Yael Bar-On & Irit Avivi

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

    Ron Ram, Odelia Amit, Ronit Gurion, Pia Raanani, Yael Bar-On, Irit Avivi & Ofir Wolach

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

    Tsila Zuckerman

  4. Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel

    Tsila Zuckerman

  5. Davidoff Cancer Center, Beilinson Hospital, Rabin Medical Center Petah Tiqva, Institute of Hematology, Petah Tikva, Israel

    Ronit Gurion, Pia Raanani & Ofir Wolach

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  1. Ron Ram
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  2. Odelia Amit
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Correspondence to Ron Ram.

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Conflict of interest

RR and OW served on an advisory board for AbbVie. OA, TZ, RG, PR, YB, and IR declare that they have no conflict of interest.

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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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Ram, R., Amit, O., Zuckerman, T. et al. Venetoclax in patients with acute myeloid leukemia refractory to hypomethylating agents—a multicenter historical prospective study. Ann Hematol 98, 1927–1932 (2019). https://doi.org/10.1007/s00277-019-03719-6

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  • DOI: https://doi.org/10.1007/s00277-019-03719-6

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