AstraZeneca has received U.S. Food and Drug Administration (FDA) approval for its CALQUENCE® (acalabrutinib) in combination with venetoclax as the first all-oral, fixed-duration regimen for adults with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in the first-line setting.
The approval marks a significant advancement in CLL treatment, offering patients a 14-month oral regimen that has demonstrated strong efficacy and a manageable safety profile.
The FDA’s decision was based on results from the AMPLIFY Phase III trial, which showed that 77% of patients treated with CALQUENCE plus venetoclax remained progression-free at three years, compared with 67% of those receiving standard chemoimmunotherapy, including fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab. The combination reduced the risk of disease progression or death by 35%, and median progression-free survival was not reached, compared with 47.6 months for chemoimmunotherapy. The trial results were presented at the 2024 American Society of Hematology Annual Meeting and published in The New England Journal of Medicine.
CALQUENCE is a selective, second-generation Bruton’s tyrosine kinase (BTK) inhibitor that disrupts B-cell proliferation, trafficking, chemotaxis, and adhesion. The drug is already approved in multiple countries for CLL and SLL, including the U.S., Europe, Japan, China, Canada, and the U.K., as well as for previously untreated mantle cell lymphoma in select markets. The new fixed-duration approval in the U.S. provides an alternative to continuous therapy, which can pose long-term side effect burdens for patients.
The approval reflects AstraZeneca’s ongoing clinical development program evaluating CALQUENCE as a standalone therapy and in combination with standard-of-care regimens for various B-cell malignancies, including CLL, mantle cell lymphoma, and diffuse large B-cell lymphoma. Regulatory filings based on the AMPLIFY trial results are underway in additional countries.
CALQUENCE plus venetoclax offers physicians a highly effective, well-tolerated option that enables treatment individualization, providing patients with a defined treatment course rather than indefinite therapy. The combination is expected to influence first-line treatment decisions for CLL and underscores the potential of targeted oral therapies to improve outcomes and convenience for patients living with blood cancers.
