Venetoclax for the treatment of mantle cell lymphoma

While the last decade has seen an explosion in improved therapies for mantle cell lymphoma (MCL), the outlook for patients with relapsed or refractory MCL (R/R MCL) remains poor, especially for those who are older with comorbidities or harbour dysfunction in the TP53 pathway. MCL is one of the B cell malignancies in which there is a high frequency of BCL2 overexpression, and the selective BCL2 inhibitor venetoclax has shown particular promise in the treatment of patients with R/R MCL. As a single agent, the drug is associated with a close to 80% response rate in early phase studies. However, secondary progression due to the development of resistance remains a limiting factor in the usefulness of this agent. Preclinical data has driven the push to combine venetoclax with other novel agents, particularly the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib. This therapeutic combination has increased the rate of complete remissions to over 60% and provides a promising route to meaningful long-term disease control with non-chemotherapy-based treatment.