BCL-2 inhibition in Waldenström macroglobulinaemia and marginal zone lymphoma

Marginal zone lymphoma (MZL) and Waldenström macroglobulinaemia (WM) are B-cell lymphomas characterized by an indolent disease course. However, both are incurable with current standard treatments. Therefore, additional therapies are certainly needed. BCL-2 inhibition has been a welcome addition to the treatment armamentarium for haematological malignancies. The BCL-2 inhibitor venetoclax is approved by the Food and Drug Administration and the European Medicines Agency for the treatment of chronic lymphocytic leukaemia and acute myeloid leukaemia and is endorsed by the National Comprehensive Cancer Network for the treatment of WM and mantle cell lymphoma. In this review, we provide an overview of the current understanding of the BCL-2 apoptotic pathway and its impact on the development and maintenance of haematological cancers. We also summarize the preclinical and ongoing clinical experience with BCL-2 inhibitors, such as venetoclax, sonrotoclax, lisaftoclax and LOXO-338. BCL-2 inhibitors have emerged as safe and effective treatment options for treating patients with MZL and WM.