A fixed-duration regimen of acalabrutinib in combination with venetoclax, with or without obinutuzumab, has been approved in the European Union (EU) for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on positive results from the pivotal AMPLIFY Phase III trial, presented at the American Society of Hematology 2024 Annual Meeting and published in The New England Journal of Medicine.

Results from the AMPLIFY trial showed 77% of patients treated with acalabrutinib plus venetoclax and 83% of patients treated with acalabrutinib plus venetoclax and obinutuzumab were progression free at three years, versus 67% of patients treated with standard-of-care chemoimmunotherapy (investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab).

Median progression-free survival (PFS) was not reached for either experimental arm versus 47.6 months for chemoimmunotherapy.

Acalabrutinib plus venetoclax reduced the risk of disease progression or death by 35% compared to chemoimmunotherapy (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87; p=0.0038). Acalabrutinib plus venetoclax with obinutuzumab demonstrated a 58% reduction in the risk of disease progression or death compared to chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001).

CLL is the most common type of leukaemia in adults. An estimated 27,000 people were diagnosed with CLL in the UK, France, Germany, Spain and Italy in 2024.3

Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany and investigator for the AMPLIFY trial, said: “For patients diagnosed with chronic lymphocytic leukaemia, this approval provides a new option in the first-line setting that may help to minimise long-term side effects and reduce drug resistance as they may occur with continuous treatment. A fixed-duration regimen is appealing to patients and helps with adherence during the treatment period.”

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Today’s approval brings a new fixed-duration treatment option to patients with previously untreated chronic lymphocytic leukaemia across Europe. Acalabrutinib plus venetoclax is the first and only all-oral combination treatment option with a second-generation BTK inhibitor approved in the EU and provides patients and their physicians more flexibility in managing this incurable blood cancer."

The safety and tolerability of acalabrutinib was consistent with its known safety profile, and no new safety signals were identified.

Regulatory applications for these regimens are currently under review in several countries based on the AMPLIFY results.

Source: AstraZeneca