Dr. Awan on Selecting BTK Inhibitors for CLL Management

Farrukh Awan, MD, professor, the Department of Internal Medicine, UT Southwestern Medical Center, member, the Division of Hematology and Oncology, Harold C. Simmons Comprehensive Cancer Center, discusses the current use of BTK inhibitors in the management of chronic lymphocytic leukemia (CLL) and important factors to consider when determining the best treatment strategy.

Cross-trial comparisons of several studies on BTK inhibitors show that ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) appear to have similar efficacy in the frontline setting. Considering this, clinicians need to evaluate the differences in toxicity between these 3 agents to select the appropriate treatment for their patients. The absence of head-to-head, first-line comparative studies can make this comparison challenging, but extrapolating data from these studies in the relapsed setting can help clinicians predict the performance of these therapies in the frontline.

Although all 3 drugs were shown to be well tolerated in this patient population, data indicatethat newer agents, specifically acalabrutinib, appear to have a slightly lower risk of toxicity compared with the older agent ibrutinib. Moreover, newer agents may have less cardiotoxicity and provide a lower risk of hypertension. Bleeding risks appear to be similar in all 3 drugs, while atrial fibrillation and ventricular arrhythmias are generally highest with ibrutinib, and progressively decline with acalabrutinib and zanubrutinib.

More long-term follow-up data are needed to conclusively distinguish between these 3 agents in clinical practice.