Review Article

Emerging Therapies in Chronic Lymphocytic Leukemia: Current Trials

Ashley E. Glode, PharmD, BCOP, and Hani M. Babiker, MD

Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences; and University of Arizona College of Medicine, Translational Genomics Research Institute, and University of Arizona Cancer Center

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

Ashley E. Glode, PharmD, BCOP, University of Colorado Anschutz Medical Campus, 12850 East Montview Blvd, Mail Stop C238, Aurora, CO 80045. E-mail: ashley.glode@ucdenver.edu


J Adv Pract Oncol 2017;8:71–86 | https://doi.org/10.6004/jadpro.2017.8.7.17 | © 2017 Harborside™


  

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults in the Western hemisphere, and in 2017, it is expected to be diagnosed in 20,110 people, with 4,660 dying of this disease. The median age at diagnosis of CLL is 72; 70% are aged 65 and older and 40% are aged 75 and older. Chronic lymphocytic leukemia is a heterogeneous disease, as some patients never require therapy and are kept under surveillance, whereas others progress through several lines of treatment, never achieving remission, and die within 2 to 3 years of diagnosis. Treatment for CLL has progressed from an era where traditional cytotoxic agents were the mainstay of treatment to an era where targeted therapies including monoclonal antibodies and small-molecule inhibitors play a key role in treatment, in addition to a new emerging role for immunotherapy. Although targeted therapies have demonstrated efficacy in CLL, some patients cannot tolerate treatment due to advanced age or significant comorbidities. Poor prognostic factors include high serum beta2-microglobulin level, 2% or less mutation in the immunoglobulin heavy-chain variable region, 30% or greater CD38 expression on flow cytometry, 20% or greater zeta-chain–associated protein 70 (ZAP-70) somatic mutation, deletion 11q, deletion 17p, lymphocyte doubling time of less than 6 months, and Rai stage III and IV disease. Despite the advances made in diagnosis and treatment, CLL still remains essentially an incurable malignancy (Masood et al., 2011). Patients with CLL also are at risk of developing Richter’s transformation (about 2%–10%), which is a histologic transformation to a more aggressive type of lymphoma (diffuse large B-cell lymphoma or Hodgkin lymphoma. The risk of transformation increases with the more lines of therapy a patient receives. The development of agents with improved outcomes and the potential for cure are needed to minimize the amount of therapy a patient receives. 




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