AstraZeneca has secured U.S. approval for a new all-oral, fixed-duration treatment regimen for adults with chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), marking a significant shift in frontline care for the most common type of adult leukaemia.
The U.S. Food and Drug Administration approved the combination of Calquence (acalabrutinib) and venetoclax based on results from the Phase III AMPLIFY trial. The findings were presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine.
The approval establishes Calquence plus venetoclax as the first all-oral, fixed-duration Bruton’s tyrosine kinase (BTK) inhibitor-based regimen available in the United States for previously untreated CLL and SLL patients. The 14-month treatment course offers an alternative to continuous therapy, which is often associated with cumulative side effects and long-term treatment burden.
In the AMPLIFY trial, 77% of patients treated with the Calquence-venetoclax combination remained progression-free at three years, compared to 67% of those receiving standard chemoimmunotherapy regimens, including fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab. Median progression-free survival was not reached in the combination arm, versus 47.6 months in the chemotherapy group. The regimen reduced the risk of disease progression or death by 35%, with a hazard ratio of 0.65 (95% confidence interval 0.49–0.87; p=0.0038), demonstrating statistically significant and clinically meaningful improvement.
CLL remains an incurable but typically slow-progressing blood cancer. Approximately 18,500 patients were treated in the first-line setting in the United States in 2024. While outcomes have improved with targeted therapies, many patients face the challenge of indefinite treatment.
Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute and Harvard Medical School, and principal investigator of the AMPLIFY study, highlighted the importance of providing an effective, time-limited option that is well tolerated and flexible enough to meet individual patient goals.
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, described the approval as a milestone that could reshape first-line treatment decisions in CLL. Patient advocacy leaders also welcomed the development, with Gwen Nichols, MD, of Blood Cancer United noting that new fixed-duration options may help reduce the psychological and physical burden of long-term therapy.
The safety profile of Calquence in combination with venetoclax was consistent with previously reported data, and no new safety concerns were identified.
The regimen has also received approval in the European Union, Canada, and the United Kingdom, with additional regulatory reviews ongoing worldwide, underscoring its growing global impact in CLL treatment.