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

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the AMPLIFY Phase III trial,

Results showed Calquence plus venetoclax reduced the risk of disease progression or death by 35% compared to standard-of-care chemoimmunotherapy (investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab; hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87; p=0.0038). Calquence plus venetoclax with obinutuzumab demonstrated a 58% reduction in the risk of disease progression or death compared to standard-of-care chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001).

At three years, 77% of patients treated with Calquence plus venetoclax and 83% of patients treated with Calquence plus venetoclax and obinutuzumab were progression free, versus 67% of patients treated with chemoimmunotherapy. Median progression-free survival (PFS) was not reached for either experimental arm versus 47.6 months for chemoimmunotherapy.

Wojciech Jurczak, MD, Maria Sklodowska-Curie National Institute of Oncology, Kraków, Poland and investigator for the trial, said: “Chronic lymphocytic leukaemia is an incurable cancer which means patients live with the disease and stay on treatment for many years, which can have long-term effects. The fixed-duration Calquence regimens will allow patients to take breaks from their treatment, reducing the risk of long-term adverse events and drug resistance.”

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “With this recommendation, Calquence plus venetoclax can potentially be the only all-oral second-generation BTK inhibitor option approved in Europe for patients with previously untreated chronic lymphocytic leukaemia. Calquence has demonstrated efficacy and safety in fixed-duration and treat-to-progression regimens providing patients and their doctors more treatment flexibility.”

CLL is the most common type of leukaemia in adults, with an estimated 27,000 patients diagnosed in the UK, France, Germany, Spain and Italy in 2024.

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

Regulatory applications for Calquence plus venetoclax, with or without obinutuzumab, in this setting are currently under review in several countries based on the AMPLIFY results.