Venetoclax for the treatment of chronic lymphocytic leukemia

ABSTRACT

Introduction: Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the United States Food and Drug Administration (FDA) for the treatment of chronic lymphocytic leukemia (CLL) patients with 17p deletion [del(17p)], who have received at least one prior therapy.

Areas covered: We focus on the mechanism of action of venetoclax and on the clinical trial data that led to the approval of venetoclax for CLL patients. We also review the studies in which this drug has being explored in combination with other anti-CLL drugs.

Expert opinion: Data from early clinical trials have shown that venetoclax, as a single agent, is highly effective for relapsed/refractory CLL patients, including those cases with high-risk features.

Furthermore, venetoclax seems to be an appropriate option for patients who progress on B-cell receptor (BCR) pathway kinase inhibitors. Venetoclax is also safe, with the most common serious adverse events being neutropenia. The risk of tumor lysis syndrome (TLS) can be reduced by a slow dose ramp-up, careful monitoring, and adequate prophylaxis. Ongoing trials will further clarify the safety and efficacy of venetoclax in combination with other drugs in both relapsed/refractory and untreated CLL patients.

KEYWORDS:

• Venetoclax
• BCL-2 inhibitor
• CLL
• therapy

Article highlights

• Since almost all CLL cells evade apoptosis through overexpression of B-cell lymphoma/leukemia 2 (BCL-2) protein, inhibition of this pathway is an attractive therapeutic target.

• Venetoclax, an orally bioavailable inhibitor of BCL-2, was approved in 2016 by the U.S. FDA for the treatment of CLL patients with 17p deletion, who have received at least one prior therapy.

• Venetoclax, as a single agent, is highly effective for relapsed/refractory CLL patients, including those cases with high-risk features.

• Venetoclax is safe, with the most common serious adverse events being neutropenia. The risk of TLS can be reduced by a slow dose ramp-up, careful monitoring, and adequate prophylaxis.

• Ongoing trials will clarify the safety and efficacy of venetoclax in combination with other drugs in both relapsed/refractory and untreated CLL patients.

Box 1. Drug summary.

Declaration of Interest

F. Morabito has received ‘microRNA-based immunotherapeutic strategies for Multiple Myeloma and Chronic Lymphocytic Leukemia’ – Innovative immunotherapeutic treatments of human cancer (MultiUnit – Multi Unit Regional 16,695/2014). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This article was not funded.