Dr. Woyach on the Safety Profiles of BTK Inhibitors in CLL

Jennifer Woyach, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center-James, discusses the safety profiles of BTK inhibitors in patients with chronic lymphocytic leukemia (CLL).

When it comes to BTK inhibitors, especially ibrutinib (Imbruvica), a lot of data are available on the long-term toxicity profiles, says Woyach. With ibrutinib, the most concerning adverse event (AE) is atrial fibrillation, which occurs in 10%-15% of patients. Other less common events include ventricular arrhythmias, which only occur in less than 1% of patients, and grade 3 or higher hypertension, which occurs in up to 30% of patients and that is typically due to long durations of therapy, explains Woyach. Additionally, some of the more common, but also less dangerous, AEs are arthralgias, fatigue, and upper-respiratory infections, adds Woyach. 

With acalabrutinib (Calquence), atrial arrythmias are sometimes reported, although these events happen less frequently than what is seen with ibrutinib, according to Woyach. Additionally, less bruising is seen with acalabrutinib, as well as fewer arthralgias. Although headaches are reported with the agent, they are mostly low grade and resolve with time.

Venetoclax (Venclexta) is another commonly used BTK inhibitor. With this agent, neutropenia are sometimes reported, especially early on in treatment, explains Woyach. Additionally, with this agent, there is also the risk of tumor lysis syndrome.

With chemoimmunotherapy, cytopenias are the most commonly reported AEs, says Woyach. Specifically, with FCR, a combination therapy comprised of fludarabine, cyclophosphamide, and rituximab (Rituxan), there is the risk of myelodysplastic syndrome and acute myeloid leukemia (AML), concludes Woyach.