AstraZeneca announced that the U.S. Food and Drug Administration has approved its fixed-duration all-oral combination of Calquence® (acalabrutinib) with venetoclax for the first-line treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in adults. The approval marks the first time a Bruton’s tyrosine kinase (BTK) inhibitor-based regimen has been authorised in the U.S. as a time-limited, oral treatment option for newly diagnosed patients.
The approval is based on positive results from the Phase III AMPLIFY trial, in which the Calquence plus venetoclax combination significantly improved progression-free survival (PFS) versus chemoimmunotherapy. At three years, 77 % of patients receiving the all-oral regimen remained progression-free, compared with 67 % in the standard-of-care arm. The 14-month fixed-duration course also reduced the risk of disease progression or death by about 35 %. Median PFS was not reached for the Calquence combo, compared with 47.6 months for patients on conventional chemotherapy.
Dave Fredrickson, Executive Vice President of the Oncology Haematology Business Unit at AstraZeneca, said the approval brings “the first all-oral, fixed-duration BTK inhibitor-based regimen” to the U.S. and has the potential to meaningfully change treatment decisions for patients and physicians. The company emphasised that the regimen’s oral dosing and defined length of therapy could offer a chemotherapy-sparing alternative that aligns with patient preferences and clinical practice trends.
CLL is the most common form of adult leukemia, with an estimated 18,500 patients treated in the first-line setting in the U.S. in 2024. The new approval follows earlier regulatory clearances for the combination in multiple global markets and adds to AstraZeneca’s expanding hematology portfolio, which focuses on innovative treatments for blood cancers.
Medical experts noted that the Calquence plus venetoclax regimen’s fixed 14-month duration and all-oral administration could lessen the long-term treatment burden compared with continuous BTK inhibitor therapy or traditional chemoimmunotherapy, providing physicians with more options to tailor care based on individual patient needs.
