Venetoclax + acalabrutinib approved by the FDA for previously untreated CLL

On February 20, 2026, the U.S. Food and Drug Administration (FDA) granted approval to venetoclax + acalabrutinib, an all-oral, fixed-duration regimen, for the treatment of previously untreated adult patients with chronic lymphocytic leukemia (CLL).¹ 

This approval is based on the results from the multi-center, open-label, phase III AMPLIFY study (NCT05197192), evaluating venetoclax + acalabrutinib ± obinutuzumab vs investigator’s choice of chemoimmunotherapy in patients with CLL without 17p deletion or TP53 mutation.¹ Results from this trial were previously reported by the Lymphoma Hub. Risk of disease progression or death was 35% lower in patients receiving venetoclax + acalabrutinib vs chemoimmunotherapy (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.49–0.87; p = 0.0038).¹ At a median follow-up of 42.6 months, median progression-free survival was not reached in patients receiving venetoclax + acalabrutinib (95% CI, 51.1 months–not reached) vs 47.6 months in patients receiving chemoimmunotherapy (95% CI, 43.3 months–not reached).¹ The safety profile of venetoclax + acalabrutinib was consistent with the known safety profile of each therapy alone.¹ The most common serious adverse events in patients receiving venetoclax + acalabrutinib were COVID-19, including COVID-19 pneumonia (9%), secondary primary malignancies (2.7%), and neutropenia (2.1%).¹