Advances in drug‐based therapies in chronic lymphocytic leukemia and future prospects

Abstract

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world, with over 20 000 new cases diagnosed in the United States each year. 1 It is characterized by a clonal expansion of CD5 positive B cells within the blood, bone marrow, lymph nodes, and spleen. 2 The disease course for patients with CLL is markedly varied with a subset of patients experiencing indolent disease that does not require therapy for decades, while others experience more rapidly progressive disease despite the multiple lines of therapy. A deeper insight into the biology of CLL has identified factors that contribute to disease heterogeneity and has paved the way for a pharmacologic revolution, with the development of a variety of highly effective and well-tolerated novel, targeted agents. As a result, using prognostic information to guide treatment selection has become a priority, in order to identify patients for whom conventional chemoimmunotherapy (CIT) remains appropriate and those for whom novel treatment approaches may provide improved outcomes. AbstractChronic lymphocytic leukemia (CLL) has experienced a revolution over the past few decades with a marked expansion in therapeutic options and improvement in outcomes. This success can be attributed to an improved understanding of the molecular and genetic underpinnings of disease pathogenesis and the emergence of a variety of effective, well-tolerated, targeted therapies. The field is now continuing to evolve with an improved understanding of prognostic and predictive biomarkers of response, exploration of novel combination strategies with the goal of inducing deeper and more durable remissions, and the development of next-generation and immunebased agents. Here, we review the recent advances in CLL therapy as well as the novel therapeutic innovations that are likely to contribute to the rapidly evolving treatment paradigms in this disease. K E Y W O R D Sacalabrutinib, chronic lymphocytic leukemia, CLL, duvelisib, ibrutinib, targeted therapy, venetoclax