Dr Brown on QOL Considerations With Frontline Acalabrutinib/Venetoclax in CLL

“The all-oral aspect [of acalabrutinib and venetoclax] will significantly improve QOL for [patients who are receiving] a frontline venetoclax-containing regimen.”

Jennifer R. Brown, MD, PhD, director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and the Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology at Harvard Medical School, discussed the recent February 2026 FDA approval of acalabrutinib (Calquence) plus venetoclax (Venclexta) for the frontline treatment of patients with chronic lymphocytic leukemia (CLL). Brown specifically commented on the combination’s ability to improve quality-of-life (QOL) for patients with CLL.

The approval was supported by the phase 3 AMPLIFY trial (NCT03836261), which evaluated the combination with or without obinutuzumab (Gazyva) vs standard-of-care chemoimmunotherapy (n = 290). Safety data from the trial showed that grade 3 or higher adverse effects (AEs) that were most common among patients in the combination arm with acalabrutinib plus venetoclax alone (n = 291) were neutropenia (32.3%), infection (12.4%), hypertension (2.7%), second primary cancer (1.7%), cardiac AEs (1.7%), hemorrhages (1%), atrial fibrillation or flutter (0.3%), and tumor lysis syndrome (0.3%).

Along with the safety profile of the combination, Brown looked to another aspect of acalabrutinib/venetoclax as the most significant for patient QOL: its all-oral formulation. Brown noted how the combination of obinutuzumab plus venetoclax has been commonly administered to patients with CLL, with obinutuzumab given as an infusion, which ultimately requires patients to travel to clinics for a total of 8 weeks, she said. However, Brown pointed out how the acalabrutinib-based combination demands far less clinic visits for patients than the obinutuzumab-based combination.

When discussing the potential safety drawbacks of acalabrutinib plus venetoclax, Brown mentioned that receiving two drugs at once might raise safety concerns, although patients should ultimately be reassured due to the promising data for the combination from AMPLIFY. Brown concluded by suggesting patients discontinue acalabrutinib before 14 months, since at this point cardiac AEs often begin to occur.