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.
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.
KeywordsChronic lymphocytic leukemia Combination therapy Ibrutinib Idelalisib Venetoclax Chimeric antigen receptor-T cells
Compliance with Ethical Standards
Conflict of Interest
Tanya Siddiqi is a speaker for Pharmacyclics/Jannsen and Seattle Genetics; consultant for Juno therapeutics, BeiGene, Pharmacyclics, and Astra Zeneca. Maliha Khan declares that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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