FDA approves acalabrutinib plus venetoclax for first-line CLL/SLL
The FDA approved acalabrutinib plus venetoclax for previously untreated CLL/SLL based on phase 3 AMPLIFY data. The fixed 14-month regimen improved progression-free survival versus chemotherapy.
The FDA has approved acalabrutinib and venetoclax for previously untreated CLL/SLL, making the combination the only all-oral, fixed-duration combination option for first-line, treatment-naïve CLL/SLL. The approval was based on phase 3 AMPLIFY trial data. A key advantage of the new protocol is its fixed 14-month duration, which offers patients a clear treatment end point and the potential for significant time off treatment.
The novel combination provided statistically significant and clinically meaningful improvement in progression-free survival versus investigator’s choice of standard-of-care chemotherapy. Even after 3 years, 77% of patients had not experienced disease progression compared with 67% who received investigator’s choice of standard-of-care chemotherapy. Median progression-free survival was not reached in the treatment cohort versus 47 months, respectively, and risk of death was reduced by an overall 35% (HR, 0.65; 95% CI, 0.49-0.87; P = .0038).
Results presented at the 2025 European Hematology Association Congress also showed that acalabrutinib and venetoclax plus obinutuzumab produced higher rates of undetectable measurable residual disease versus chemoimmunotherapy as measured via flow cytometry and next-generation sequencing in the 3 treatment arms. These rates were 95% for acalabrutinib and venetoclax plus obinutuzumab, 45% for acalabrutinib and venetoclax, and 73% for FCR/BR, and the differences remained evident for up to 36 months after therapy ended.
The safety profile remained consistent with the known adverse effects of the individual medications. Common adverse events seen in at least 2% of patients who received the combination included COVID-19 and COVID-19 pneumonia (9%), second primary malignancies (2.7%), and neutropenia (2.1%); incidence of tumor lysis syndrome was 0.3%.
Acalabrutinib plus venetoclax is now approved in the US, the European Union, Canada, and the United Kingdom, and additional regulatory applications are under review.