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

Lew, TE; Seymour, JF

Author(s): Lew, TE; Seymour, JF;
Details: Publication Year 2022-06-03,Volume 15,Issue #1,Page 75
Journal Title: Journal of Hematology & Oncology
Abstract: 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.
Publisher: BMC
Keywords: Adult; *Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic/pharmacology/therapeutic use; Humans; *Lymphoma, B-Cell/drug therapy; *Multiple Myeloma/drug therapy; Proto-Oncogene Proteins c-bcl-2/metabolism; Sulfonamides/pharmacology/therapeutic use; Apoptosis; Bcl2; Chronic lymphocytic leukemia; Lymphoma; Multiple myeloma; Navitoclax; Non-Hodgkin lymphoma; Programmed cell death; Venetoclax
Research Division(s): Blood Cells And Blood Cancer
PubMed ID: 35659041
Publisher's Version: https://doi.org/10.1186/s13045-022-01295-3
Open Access at Publisher's Site: https://doi.org/10.1186/s13045-022-01295-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-02-02 02:06:31

Last Modified: 2023-02-02 02:11:27