An update on the efficacy of Venetoclax for chronic lymphocytic leukemia

The BCL2 inhibitor venetoclax has dramatically changed the treatment of chronic lymphocytic leukemia (CLL) and has introduced the concept of time-limited therapy with targeted agents.

This review discusses the mechanism of action of venetoclax, adverse effects, and the clinical data with this agent as identified by a selective search of clinical trials in the PubMed database. Venetoclax is FDA-approved with anti-CD20 monoclonal antibodies; however, research is ongoing evaluating its efficacy when given in combination with other agents, such as the Bruton's Tyrosine Kinase (BTK) inhibitors.

Venetoclax-based therapy is an excellent treatment option for patients interested in time-limited therapy and can be offered in both the front-line and relapsed/refractory settings. Tumor lysis syndrome (TLS) risk evaluation, preventative measures, and strict monitoring should be conducted, while these patients ramp up to target dose. Venetoclax-based therapies produce deep and durable responses with patients often achieving undetectable measurable residual disease (uMRD). This has led to a discussion of MRD-driven, finite-duration treatment approaches, although longer term data is still needed. While many patients eventually lose uMRD status, re-treatment with venetoclax remains an area of interest with promising results. Mechanisms of resistance to venetoclax are being elucidated, and research is ongoing.