Review Article

Small Molecules in Chronic Lymphocytic Leukemia: Novel Targets, New Challenges

Sandra E. Kurtin, PhDc, ANP-C, AOCN®, and Ali McBride, PharmD, BCOP

The University of Arizona Cancer Center, Tucson, Arizona

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

Sandra E. Kurtin, PhDc, ANP-C, AOCN®, The University of Arizona Cancer Center, 3838 North Campbell Avenue, Tucson, AZ 85719. E-mail:

J Adv Pract Oncol 2017;8:55–69 | | © 2017 Harborside™



The treatment of chronic lymphocytic leukemia (CLL) is in a state of transformation owing largely to an improved understanding of the pathways and molecular targets in normal B-cell development, the role aberrant pathways play in the development of B-cell malignancies, and how these aberrations can be exploited for therapeutic benefit. Small-molecule agents are among the new agents recently approved for the treatment of CLL. Understanding the individual mechanisms of action provides a critical foundation for the advanced practitioner (AP) necessary for the safe and effective administration of small-molecule agents. The goals of this paper are to highlight the B-cell receptor and associated pathways, the B-cell lymphoma 2 family of proteins, and the tumor microenvironment with discussion of agents targeting these pathways currently approved for the treatment of CLL. Highlights from pivotal clinical trials including drug properties, specific administration requirements, management and mitigation of adverse events, and application of the experience gained from clinical trials are included. The currently approved small-molecule agents for CLL are oral therapies. Given the significant role APs play in the management of adverse events (AEs) and emergent outpatient visits to avoid emergency department visits or hospitalization, AE management will be highlighted. 

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