Dr Brown on Notable Design Features of the AMPLIFY Trial in CLL

“We have strategies to manage [these toxicities], where we can give patients anti-emetics as premedication.”

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 phase 3 AMPLIFY trial (NCT03836261) that supported the FDA approval of acalabrutinib (Calquence) plus venetoclax (Venclexta) for chronic lymphocytic leukemia in February 2026. In addition to discussing the trial’s design, Brown also overviewed safety data for the combination.

Brown began by laying out core aspects of AMPLIFY, noting how it was a phase 3, international trial that evaluated the combination with or without obinutuzumab (Gazyva) vs chemoimmunotherapy. Before diving into safety, she mentioned the improvements in progression-free survival (PFS) that the combination of acalabrutinib plus venetoclax showed in comparison to chemoimmunotherapy. The combination arm of the trial (n = 291) demonstrated a 3-year PFS rate of 76.5% (95% CI, 71.0%-81.1%) compared with 66.5% (95% CI, 59.8%-72.3%) in the chemoimmunotherapy arm (n = 290).

Brown then pointed out how patients in the trial experienced high rates of infections, which could possibly be attributed to the COVID-19 pandemic occurring concurrently with AMPLIFY. Outside of infections, Brown discussed how the combination was well-tolerated and manageable, especially considering how much experience clinicians have with venetoclax. Administering anti-emetics as pre-medications are a viable strategy in combating common adverse effects (AEs) with venetoclax such as nausea, she added. Other grade 3 or higher AEs that were commonly reported with patients who received the combination in the trial 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%).

Brown concluded by reassuring that patients do well with the combination, noting how many AEs like low blood counts, neutropenia, and tumor lysis syndrome are often resolved within patients.