Evolution of CLL treatment — from chemoimmunotherapy to targeted and individualized therapy

During the past 5 years, a number of highly active novel agents, including kinase inhibitors targeting BTK or PI3Kδ, an antagonist of the antiapoptotic protein BCL-2, and new anti-CD20 monoclonal antibodies, have been added to the therapeutic armamentarium for patients with chronic lymphocytic leukaemia (CLL). In these exciting times, care is needed to optimally integrate these novel agents into the traditional treatment algorithm without overlooking or compromising the benefits of established treatments, especially chemoimmunotherapy. A more personalized approach to CLL therapy that takes into account individual risk factors, patient characteristics, and their treatment preferences is now possible. Herein, we discuss the biological basis for the novel therapeutic agents and outline not only the major advantages of these agents over traditional therapies but also their adverse effects and the rationale for continued use of older versus newer types of therapy for selected patients with CLL. We conclude by providing recommendations for an individualized therapy approach for different populations of patients with CLL.