Holding the therapy in CLLp53: mechanisms to achieve durable responses

Chronic lymphocytic leukemia (CLL) is a common leukemia, mainly affecting the elderly. Originating in the bone marrow, CLL involves the accumulation of B lymphocytes and progresses slowly, though 50-60% of patients will require therapy. At diagnosis, the presence of p53 protein aberrations, such as 17p deletion and TP53 mutation, arises in approximately one out of 10 patients. Even in the era of targeted therapies, these aberrations remain the most important prognostic factors. Current guidelines favor continuous BTK inhibitor therapy in patients with CLLp53, though adverse events and drug resistance may lead to discontinuation. Herein, we discuss the effects of B-cell receptor and BCL-2 inhibition, as well as the role of the immune system, in two elderly CLLp53 patients with prolonged responses to different therapies.