Balancing Efficacy and Safety in CLL Treatment with BTK Inhibitors

In a recent live discussion, Dr. Andrew H. Lipsky, an assistant professor at Columbia University Medical Center and hematologist/oncologist at Columbia University Herbert Irving Comprehensive Cancer Center, led a Case-Based Roundtable with community oncologists from North and South Carolina to explore treatment strategies for treatment-naïve chronic lymphocytic leukemia (CLL). The focus of this dialogue was on the use of Bruton’s tyrosine kinase (BTK) inhibitors—specifically acalabrutinib (Calquence) and zanubrutinib (Brukinsa)—in comparison to venetoclax (Venclexta)-based regimens. The participants discussed critical factors such as efficacy, safety, patient preferences, dosing flexibility, and the challenges associated with treatment delivery in community settings.

Chronic lymphocytic leukemia, a common form of leukemia in adults, necessitates careful treatment planning, particularly for patients who are new to therapy. The group deliberated on the findings from the ELEVATE TN trial, which compared acalabrutinib alone and in combination with obinutuzumab (Gazyva) against chlorambucil and obinutuzumab. This trial highlighted the importance of considering patient-specific factors and comorbidities when selecting the optimal treatment regimen (Sharman et al., 2020).

Dr. Margaret Howard, an oncologist with extensive experience in CLL, emphasized the need to assess the burden of disease within specific patient populations, advocating for dual-agent therapy in certain cases. "The decision should consider the individual patient's profile and potential comorbidities," she stated, referencing the importance of personalized medicine in oncology.

Dr. Charles Kuzma shared insights on the practical challenges of treatment options, noting that many patients prefer therapies that do not require intravenous administration, particularly in rural settings where access to healthcare can be limited. "Patients often opt for oral treatments like BTK inhibitors due to the convenience and the avoidance of potential adverse effects associated with intravenous therapies," Kuzma explained.

Dr. Viral Rabara pointed out that many patients do not require the full dose of BTK inhibitors to achieve therapeutic effects, suggesting that starting at a lower dosage can mitigate adverse events. This is particularly relevant for older patients or those with significant comorbidities. "In my practice, I often initiate treatment at a reduced dose, which allows for better patient tolerance and adherence," he noted.

Conversely, Dr. Alexandra Stefanovic from Duke Cancer Center emphasized the importance of logistical considerations when selecting treatment. "For our patients who travel long distances, BTK inhibitors are more straightforward to manage compared to venetoclax, which might lead to complications requiring more intensive monitoring," she stated. This highlights the need for oncologists to consider not just clinical efficacy but also the practicality of treatment options.

The discussion also touched upon the evolving landscape of CLL treatment, particularly with the approval of zanubrutinib, which offers a once-daily dosing option that many oncologists find beneficial for patient compliance. Dr. Anusha R. Madadi indicated a preference for zanubrutinib due to its favorable tolerance profile, particularly in older patients who may struggle with more frequent dosing regimens.

As the conversation progressed, the oncologists acknowledged the significance of incorporating patient preferences into treatment decisions. Dr. Lipsky concluded, "Understanding a patient's lifestyle and preferences is crucial. For some, the appeal of a time-limited approach with venetoclax may outweigh the convenience of continuous BTK inhibition. Our goal is to tailor the treatment to each individual, considering both clinical data and personal values."

The findings from this roundtable discussion underscore the importance of a patient-centered approach in CLL treatment, particularly in community settings where oncologists face unique challenges in delivering care. As research continues to evolve and new therapies emerge, ongoing discussions among healthcare providers will be essential to navigate the complex landscape of CLL management effectively.