Clinical experiences with venetoclax and other pro-apoptotic agents in lymphoid malignancies: lessons from monotherapy and chemotherapy combination.

Autor: Lew TE; Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.; Blood Cells and Blood Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Seymour JF; Department of Clinical Haematology, The Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia. john.seymour@petermac.org.; Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Australia. john.seymour@petermac.org.
Jazyk: angličtina
Zdroj: Journal of hematology & oncology [J Hematol Oncol] 2022 Jun 03; Vol. 15 (1), pp. 75. Date of Electronic Publication: 2022 Jun 03.
DOI: 10.1186/s13045-022-01295-3
Abstrakt: BH3-mimetics are a novel drug class of small molecule inhibitors of BCL2 family proteins which restore apoptosis in malignant cells. The only currently approved BH3-mimetic, the selective BCL2 inhibitor venetoclax, is highly efficacious in chronic lymphocytic leukemia and has rapidly advanced to an approved standard of care in frontline and relapsed disease in combination with anti-CD20 monoclonal antibodies. In this context, tumour lysis syndrome and myelosuppression are the most commonly encountered toxicities and are readily manageable with established protocols. Venetoclax is active in other lymphoid malignancies including several B cell non-Hodgkin lymphomas, acute lymphoblastic leukemia and multiple myeloma, with the highest intrinsic sensitivity observed in mantle cell lymphoma and Waldenstrom macroglobulinemia. Venetoclax combination with standard regimens in follicular lymphoma, multiple myeloma and aggressive B cell neoplasms has shown some promise, but further studies are required to optimize dose and scheduling to mitigate increased myelosuppression and infection risk, and to find validated biomarkers of venetoclax sensitivity. Future research will focus on overcoming venetoclax resistance, targeting other BCL2 family members and the rational design of synergistic combinations.
(© 2022. The Author(s).)
Databáze: MEDLINE
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