A fixed-duration combination therapy of acalabrutinib and venetoclax demonstrated superior progression-free survival compared to standard chemoimmunotherapy in previously untreated chronic lymphocytic leukemia (CLL), according to results from the Phase III AMPLIFY trial presented at the American Society of Hematology (ASH) 2024 Annual Meeting.
The trial showed that the combination of AstraZeneca’s Calquence (acalabrutinib) and venetoclax reduced the risk of disease progression or death by 35% versus standard-of-care chemoimmunotherapy, with a hazard ratio of 0.65 (95% confidence interval 0.49-0.87; p=0.0038) at a median follow-up of 41 months. When combined with obinutuzumab, the Calquence and venetoclax regimen demonstrated a 58% reduction in the risk of disease progression or death compared to chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001).
Notably, median progression-free survival was not reached for either experimental arm, while the chemoimmunotherapy arm had a median PFS of 47.6 months. Interim overall survival data indicated a favorable trend for the Calquence plus venetoclax arm (HR 0.33; 95% CI 0.18-0.56; p<0.0001), though researchers noted the OS data were immature and will continue to be assessed.
The AMPLIFY trial is the first randomized study to evaluate a fixed-duration regimen of venetoclax with a second-generation Bruton’s tyrosine kinase inhibitor (BTKi), acalabrutinib. The results position the combination as a potential first-line, all-oral, fixed-duration treatment option for patients with CLL. 77% of patients treated with Calquence plus venetoclax remained progression-free at three years.
The trial, NCT05197192, is ongoing to further assess overall survival as a key secondary endpoint.
