Dr Dorritie on Unanswered Questions Regarding Upfront Treatment Selection in CLL

Kathleen A. Dorritie, MD, hematologist/medical oncologist, the University of Pittsburgh Medical Center’s Hillman Cancer Center; assistant professor of medicine, Division of Oncology, Department of Medicine, University of Pittsburgh, discusses persistent unmet needs and unanswered questions regarding upfront treatment selection in chronic lymphocytic leukemia (CLL).

A pressing question within the treatment of CLL is determining the optimal up-front treatment for patients, Dorritie begins. Ongoing debate also currently surrounds whether it is more beneficial to administer a BTK inhibitor as a fixed-duration regimen alongside a CD20 monoclonal antibody, or to opt for venetoclax plus a monoclonal antibody, she expands.

The emergence of data supporting the use of ibrutinib (Imbruvica) and venetoclax (Venclexta), adds another layer of complexity to treatment decision-making in this setting, Dorritie continues. Prior to the read out of these data, the general consensus was to administer BTK inhibitors as a continuous therapy, Dorritie says. This approach facilitated straightforward discussions with patients about their preference for long-term BTK inhibitor therapy vs a fixed-duration treatment.

However, recent data complicates this narrative by showing that administering ibrutinib in combination with venetoclax—both targeted, oral agents—can yield high response rates and allow for treatment discontinuation, with the option for patients to resume treatment upon disease progression, Dorritie explains. In light of this development, a reevaluation of treatment strategies and consideration of the benefits of continuous vs fixed-duration approaches is necessary, she emphasizes.

Another unanswered question surrounds the potential impact of using highly potent drugs in the upfront setting on future later-line treatment strategies, Dorritie states. If the strongest therapies are utilized initially, the arsenal may be depleted for later stages of the disease, potentially limiting the options available for patients who relapse or experience disease progression, Dorritie concludes.

This underscores the complexity of personalized treatment planning in CLL, and both immediate efficacy and long-term strategy must be considered when determining the most effective and sustainable approaches for each patient.