Targeted Therapies in CLL: Monotherapy Versus Combination Approaches.

PURPOSE OF REVIEW: While chemoimmunotherapy has improved outcomes in chronic lymphocytic leukemia (CLL), it is not curative, has significant relapse rates, and is not always well tolerated. Recently, novel targeted therapies have been developed to increase response rates and reduce toxicity, especially in high-risk disease. Current goals of CLL therapies are to produce deep and durable, especially minimal residual disease (MRD)-negative, remissions so as to allow patients to ultimately discontinue treatment for a while. Whether this can be achieved with single agents or combination regimens is being investigated. Here, we comment on what the results of recent and ongoing clinical trials mean for the future of CLL therapy.

RECENT FINDINGS: Large trials have proven the efficacy of novel therapies including small-molecule inhibitors like ibrutinib, idelalisib, and venetoclax. These agents are approved as monotherapy for first-line treatment and/or in the relapsed/refractory setting. However, it appears that combining these drugs with other novel agents or with chemoimmunotherapy can give higher rates of MRD-negative remission, and delay disease resistance. Chimeric antigen receptor-T cells may change the outlook for patients with heavily refractory CLL. Further research will determine which drug combinations are optimal for the various subgroups of CLL patients.