EU Approves Calquence with Chemoimmunotherapy as First BTK Inhibitor for First-Line Mantle Cell Lymphoma

AstraZeneca's Calquence (acalabrutinib), in conjunction with bendamustine and rituximab, has been granted approval by the European Union for treating adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for an autologous stem cell transplant. This approval by the European Commission came after a positive recommendation from the Committee for Medicinal Products for Human Use and was supported by successful outcomes from the ECHO Phase III trial. These findings were showcased at the European Haematology Association (EHA) 2024 Congress and published in The Journal of Clinical Oncology. The trial results demonstrated that the combination therapy reduced the risk of disease progression or death by 27% compared to the traditional chemoimmunotherapy, with a hazard ratio of 0.73 and a 95% confidence interval of 0.57-0.94, achieving statistical significance with a p-value of 0.016. The median progression-free survival for those treated with the Calquence combination was 66.4 months, as opposed to 49.6 months with chemoimmunotherapy alone.

Mantle cell lymphoma is an uncommon and typically aggressive type of non-Hodgkin lymphoma, often diagnosed at a later stage. In 2024, approximately 6,000 cases were identified in the UK, France, Germany, Spain, and Italy. Dr. Martin Dreyling from the Department of Medicine at University Hospital LMU Munich, who was involved in the trial, emphasized that this approval offers a new initial treatment option for patients in the EU with mantle cell lymphoma. Dr. Dreyling highlighted that the combination therapy results in a significant improvement in progression-free survival, adding over 16 months for patients, which marks a considerable advancement in this challenging condition.

Dave Fredrickson, Executive Vice President of the Oncology Haematology Business Unit at AstraZeneca, expressed that the Calquence combination showed a notable enhancement in progression-free survival and maintained a consistent safety profile for patients in the pivotal ECHO trial. As the first and only BTK inhibitor approved for this condition in the EU, Fredrickson underscored the importance of providing a much-needed new option for patients grappling with this difficult disease. The safety and tolerability of Calquence were in line with its established safety profile, with no new safety signals identified.

Calquence, coupled with bendamustine and rituximab, is not only approved in the US but also in several other countries based on the ECHO trial results. Presently, regulatory applications are being reviewed in Japan and several other countries for this indication. This recent approval follows the earlier approval of Calquence for monotherapy in the treatment of adult patients with relapsed or refractory MCL in the EU.

The ECHO trial was a randomized, double-blind, placebo-controlled, multi-center Phase III study that assessed the efficacy and safety of Calquence in combination with bendamustine and rituximab, as opposed to standard-of-care chemoimmunotherapy. The trial included adult participants aged 65 and older with previously untreated MCL. Patients were divided in a 1:1 ratio to either receive Calquence or a placebo orally, administered twice daily until disease progression or unacceptable toxicity occurred. Additionally, all participants underwent six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1, followed by two years of rituximab maintenance if they responded positively to the induction therapy. The primary endpoint focused on progression-free survival, with additional endpoints including overall survival, response rates, and time to response. The trial spanned 27 countries, including nations in North and South America, Europe, Asia, and Oceania, and enrolled patients from May 2017 through March 2023, even amid the COVID-19 pandemic.