Targeted therapies may be ‘game changer’ for CLL treatment

The next step in research is to evaluate strategies to eliminate the rest of the disease while patients are on treatment, particularly for patients whom you wish to achieve long-term disease control. This may ultimately include combining or sequencing with chemotherapy or chemoimmunotherapy, or some of the newer, novel strategies, such as bispecific monoclonal antibodies or cellular therapy.


William G. Wierda, MD, PhD, is a professor in the department of leukemia within the division of cancer medicine at The University of Texas MD Anderson Cancer Center. He can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email: Disclosure: Wierda reports advisory board, consultant and speaker roles with AbbVie, Celgene, Genentech, Gilead and Pharmacyclics.


It is possible, but many patients may opt for the convenience and tolerability of an oral targeted agent.

Jonathon B. Cohen, MD, MS 

Jonathon B. Cohen

Decades of experience have confirmed that chemotherapy alone is unable to cure chronic lymphocytic leukemia, and alternative therapies are needed to improve outcomes.

In recent years, studies incorporating agents that target the B-cell receptor signaling pathway have identified promising new agents that are effective and well tolerated. Although these agents are not curative, they can be administered over many months with a low rate of relapse and herald a new era in the management of CLL.

Ibrutinib (Imbruvica, Pharmacyclics and Janssen), a Bruton’s tyrosine kinase inhibitor, and idelalisib (Gilead Sciences), a PI3K inhibitor, both demonstrate promising response rates and allow prolonged administration when administered as monotherapy, and other agents are under development and in early phase studies.

Numerous combinations with chemoimmunotherapy have been proposed and evaluated using both of these and other targeted agents. These combinations result in impressive response rates, better than what has been reported in the single-agent setting. However, the incorporation of cytotoxic chemotherapeutic agents can be associated with increased myelosuppression and non-hematologic toxicity, potentially resulting in a failure to complete all planned therapy and resulting in inferior outcomes.

In contrast to conventional chemotherapy, CD20-directed immunotherapy may improve response rate and remission durations, and it presents a viable option for therapy both as induction and maintenance because the available therapies are generally well tolerated. Randomized studies comparing monotherapy with oral targeted agents with combinations are ongoing and will hopefully provide guidance. As monoclonal antibodies to CD20+ represent targeted therapy in their own right, they serve as a logical partner with the oral targeted agents.

The integration of targeted therapies into the management of CLL is exciting but fraught with challenges, as we must determine the optimal method of administration and duration of treatment. Although combination regimens may improve the response rate over monotherapy, many patients with CLL may opt for the convenience and tolerability of an oral targeted agent, deferring chemoimmunotherapy for future therapies.

Jonathon B. Cohen, MD, MS, is a hematologist at Winship Cancer Institute of Emory University, as well as an assistant professor in hematology and medical oncology at the Emory University School of Medicine. He can be reached at The Winship Cancer Institute of Emory University, 1365C Clifton Road, Atlanta, GA 30322; email: Disclosure: Cohen reports no relevant financial disclosures.