Fixed-duration acalabrutinib plus venetoclax with or without obinutuzumab improved progression-free survival over fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab in treatment-naïve chronic lymphocytic leukemia (TN CLL), according to the results of the AMPLIFY trial.
The results were published on February 5, 2025, in the New England Journal of Medicine by a team led by Jennifer R. Brown, M.D., PhD. An interim analysis had previously been presented by Dr. Brown at the 66th American Society of Hematology Annual Meeting and Exposition held December 7-10, 2024 in San Diego, California.
AMPLIFY is the first randomized study to evaluate a fixed-duration regimen of venetoclax with a second-generation Bruton tyrosine kinase inhibitor (BTKi), according to the authors.
The trial assessed the efficacy and safety of fixed-duration acalabrutinib-venetoclax (±obinutuzumab) vs the investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab per standard dosing protocol in fit patients with TN CLL.
Estimated 36-month progression-free survival at a median follow-up of 40.8 months was 76.5% with acalabrutinib–venetoclax (P=0.004), 83.1% with acalabrutinib–venetoclax–obinutuzumab (P<0.001), and 66.5% with chemoimmunotherapy. Estimated 36-month overall survival was 94.1% with acalabrutinib–venetoclax, 87.7% with acalabrutinib–venetoclax–obinutuzumab, and 85.9% with chemoimmunotherapy.
Neutropenia, the most common adverse event of clinical interest of grade 3 or higher, was reported in 32.3%, 46.1%, and 43.2% in the three groups, respectively; death from COVID-19 was reported in 10, 25, and 21 patients in the three groups.
“Acalabrutinib–venetoclax with or without obinutuzumab significantly prolonged progression-free survival as compared with chemoimmunotherapy in fit patients with previously untreated CLL,” the authors concluded.
Reference
Brown JR, Seymour J, Jurczak W. et al. Fixed-duration acalabrutinib combinations in untreated chronic lymphocytic leukemia. N Engl J Med. 2025; doi:10.1056/NEJMoa2409804
