Ven the dose matters: Venetoclax dosing in the frontline treatment of AML.

Older/unfit adults with AML have worse outcomes and fewer treatment options than their younger/fit counterparts. In vitro studies have found a synergistic effect of hypomethylating agents (HMA) with venetoclax (VEN) on AML cells and since the phase 3 VIALE-A trial demonstrated a survival benefit, HMA + VEN has become the standard of care in the frontline setting for older/unfit adults with AML. Unfortunately, the standard 28-day cycle of VEN is associated with a high degree of myelosuppression leading to treatment delays and dose modifications. Many small retrospective studies have successfully shown comparable outcomes to VIALE-A with reduced dose/duration of VEN. Furthermore, low dose metronomic dosing of HMA + VEN has shown clinical benefit while minimizing myelotoxicity. Future trials are vital to understand the appropriate dose of VEN in combination with HMA, to evaluate HMA + VEN compared to intensive therapy for younger/fit patients, and to explore its utility in the relapsed/refractory setting.
Competing Interests: Declaration of competing interest Hannah Levavi receives consulting fees from Sobi. Keith Pratz receives research funding from AbbVie, Agios, Daiichi Sankyo, Millennium; advisory board member for AbbVie, Astellas, AstraZeneca, Boston Biomedical, Bristol Myers Squibb, Celgene, Novartis, Roche, Jazz Pharmaceuticals, and Servier. Douglas Tremblay receives contracted research funding paid to his institution from Sobi, Sumitomo, Cogent Biosciences and Gilead and consulting fees from Sobi, Novartis, AbbVie, Pharmaessentia, Sierra Oncology, GSK and Cogent Biosciences. All other authors have no conflicts of interest to disclose.
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