The Ongoing Unmet Needs in Chronic Lymphocytic Leukemia: TP53 Disruption, Richter, and Beyond

Despite recent success in regard to targeted therapies in chronic lymphocytic leukemia (CLL), patients with TP53 disruption (including deletion and/or mutation) continue to have poor outcomes compared with other patients with CLL. In this article, a review of common TP53 mutations in CLL, and recent trials using novel targeted agents in CLL patients with TP53 disruption, is provided with the goal of emphasizing the need to continuously focus on this area of research. In addition, limited but available data on double refractory CLL to BTK inhibitor and BCL-2 inhibitor, and on Richter syndrome, are reviewed.