Treatment algorithm for Japanese patients with chronic lymphocytic leukemia in the era of novel targeted therapies

Treatment for patients with chronic lymphocytic leukemia (CLL) is becoming more individualized due to the recent introduction of novel molecularly targeted therapies into the therapeutic armamentarium. Genomic and molecular risk factors in CLL patients determine the individual risk for disease progression and response to therapy, and can impact survival. In this review article, we discuss current treatment strategies for CLL patients in Japan, where the novel targeted agents, the BTK inhibitor ibrutinib and BCL2 antagonist venetoclax, now are available and increasingly used in clinical practice. We also discuss the importance of CLL risk factors for making therapy decisions, focusing on immunoglobulin variable region heavy chain (IGHV) mutation status, 11q deletion, and 17p deletion. Treatment approaches for CLL have rapidly changed in the past few years because of these new targeted agents. They are highly effective, well tolerated, and have been demonstrated in a series of large randomized clinical trials to improve survival when compared with conventional chemotherapy-based treatment. Therefore, for most patients, especially high-risk CLL patients, BTK inhibitor and BCL2 antagonist therapies are preferred over chemo-immunotherapy. Currently ongoing studies seek to determine the best sequence for these new agents and whether a combination therapy approach is beneficial. With these developments, a new era of chemotherapy-free treatment for CLL patients is expected.