The U.S. Food and Drug Administration (FDA) has granted approval for AstraZeneca’s CALQUENCE (acalabrutinib) in combination with venetoclax as a fixed-duration, all-oral treatment for adults diagnosed with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This decision is a significant milestone in the treatment of these conditions, marking an advancement in patient care options.
The approval is founded on the results of the Phase III AMPLIFY trial, which were presented at the American Society of Hematology 2024 Annual Meeting and subsequently published in The New England Journal of Medicine. CLL is recognized as the most common form of leukemia among adults, with approximately 18,500 patients receiving treatment in the first-line setting in the United States in 2024, according to AstraZeneca.
In the AMPLIFY trial, a notable 77% of patients receiving CALQUENCE combined with venetoclax remained progression-free after three years. In contrast, 67% of patients who were treated with standard chemotherapy regimens experienced similar outcomes. The combination therapy showed remarkable efficacy with the median progression-free survival not yet reached, while the chemoimmunotherapy regimen had a median of 47.6 months. Furthermore, this combination reduced the risk of disease progression or death by 35% compared to traditional chemotherapy, yielding a hazard ratio of 0.65 with a 95% confidence interval of 0.49 to 0.87 and a p-value of 0.0038.
Jennifer Brown, the principal investigator of the AMPLIFY trial and director of the CLL Center at the Dana-Farber Cancer Institute, emphasized the significance of this approval, stating, “The US approval of the CALQUENCE combination offers patients an all-oral, 14-month, fixed-duration treatment option that is highly effective and well-tolerated.”
Dave Fredrickson, executive vice president of AstraZeneca’s Oncology Haematology Business Unit, noted that this approval represents the first fixed-duration regimen in the United States based on a BTK inhibitor for first-line CLL treatment. The combination of CALQUENCE and venetoclax has also gained approval in the European Union, Canada, and the United Kingdom, with applications currently under review in additional countries.
The introduction of CALQUENCE paired with venetoclax provides a promising new avenue for patients grappling with CLL and SLL, enhancing treatment options and potentially improving patient outcomes in this challenging landscape of hematological cancers.
