Comparing Toxicity Profiles of Available Frontline Agents in CLL

Jennifer Woyach, MD, associate professor, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–James, discusses the adverse events (AEs) that differentiate the toxicity profiles of the treatments that are available in the frontline setting for patients with chronic lymphocytic leukemia (CLL).

With BTK inhibitors, specifically ibrutinib (Imbruvica), the long-term safety profiles are known, Woyach notes. The toxicities of concern with these therapies include atrial arrhythmias, which occurs in about 10% to 15% of patients with CLL. Grade 3 or greater hypertension can also occur, but that happens more frequently with longer duration of therapy. Other AEs that are less dangerous but more common include arthralgias, fatigue, and upper-respiratory infections.

Atrial arrythmias may be seen with acalabrutinib (Calquence), another BTK inhibitor, but it appears to be less frequent than with ibrutinib, Woyach says. There also appears to be less bruising and less arthralgias with acalabrutinib as well. Acalabrutinib is associated with headache, but it is predominantly low grade and goes away over time.

Venetoclax (Venclexta) is associated with neutropenia, especially early on in patients with CLL. There is also risk of tumor lysis syndrome, particularly among those with the first ramp-ups. The primary concerns with chemoimmunotherapy are cytopenias, which can occur both during and prolonged after treatment. Woyach also notes that patients treated with fludarabine, cyclophosphamide, and rituximab (Rituxan) have almost a 5% risk of myelodysplastic syndrome or acute myeloid leukemia.

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