AstraZeneca has received approval from the U.S. Food and Drug Administration for its Calquence (acalabrutinib) in combination with venetoclax as the first all-oral, fixed-duration regimen for the treatment of adult patients with Chronic Lymphocytic Leukaemia (CLL) and Small Lymphocytic Lymphoma (SLL) in the United States.

The approval is based on results from the Phase III AMPLIFY trial, which were presented at the American Society of Hematology 2024 Annual Meeting and simultaneously published in The New England Journal of Medicine.

Chronic lymphocytic leukaemia is the most common form of leukaemia in adults. In 2024, an estimated 18,500 patients in the US were treated in the first-line setting. The newly approved regimen offers a 14-month, chemotherapy-free treatment option, addressing the burden associated with continuous therapies that are often linked to long-term side effects.

In the AMPLIFY study, 77 percent of patients treated with Calquence plus venetoclax remained progression-free at three years, compared with 67percent of those receiving standard chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab). Median progression-free survival (PFS) was not reached in the combination arm versus 47.6 months for chemotherapy. The regimen reduced the risk of disease progression or death by 35 percent compared with chemoimmunotherapy.

Jennifer Brown, MD, PhD, principal investigator of the AMPLIFY trial and director of the CLL Centre at Dana-Farber Cancer Institute, said the approval provides patients with a highly effective and well-tolerated fixed-duration alternative that allows physicians greater flexibility in personalising treatment strategies.

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit at AstraZeneca, said the approval marks the first all-oral, fixed-duration BTK inhibitor-based regimen for CLL in the US and could significantly influence first-line treatment decisions.

The safety profile of Calquence in combination with venetoclax was consistent with known data, with no new safety signals identified.

The AMPLIFY trial was a global, randomised, open-label study conducted across 27 countries between 2019 and 2021. It evaluated Calquence plus venetoclax, with or without obinutuzumab, against the investigator's choice of chemoimmunotherapy in previously untreated CLL patients without del(17p) or TP53 mutation.

Calquence is a second-generation Bruton’s Tyrosine Kinase (BTK) inhibitor that blocks B-cell receptor signalling pathways critical to the growth and survival of malignant B cells. The combination regimen has already received approvals in the European Union, Canada, the UK and several other countries, with additional regulatory reviews ongoing.

AstraZeneca continues to expand its haematology portfolio, including ongoing clinical development of Calquence across multiple B-cell malignancies, as part of its broader oncology strategy aimed at transforming outcomes in blood cancers.