Debate: What Is Optimal First-Line Therapy for Chronic Lymphocytic Leukemia?

In the era of newer, highly effective targeted therapies for chronic lymphocytic leukemia ( CLL), experts debated whether there is still a role for chemoimmunotherapy in the first- line setting for the treatment of this disease. In general, targeted therapies are preferred as first-line treatment for all patients, with the exception of low-risk patients [younger, fit patients with mutated IGHV who are candidates for fludarabine/cyclophosphamide/rituximab (FCR)]. About 37% of low-risk patients experience long-term durable remissions and remain stable after treatment with FCR for many years. Advantages of FCR over small molecule inhibitors include cost, fixed duration treatment, and long-term survival benefit. Disadvantages are an etimated 5% risk of developing myelodysplastic syndrome or acute myeloid leukemia. Advantages of small molecule inhibitors are improvements in progression-free and overall survival and quality of life when compared with chemoimmunotherapy. Disadvantages of small molecule inhibitors are high cost and the need for continuous treatment. However, studies are underway to develop fixed duration regimens with combinations of small molecule inhibitors that aim to deepen remissions.