EU approves Calquence Combo

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 ECHO Phase III trial, presented at the European Haematology Association (EHA) 2024 Congress and published in The Journal of Clinical Oncology, which demonstrated that Calquence plus bendamustine and rituximab reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.57-0.94; p=0.016). Median progression-free survival (PFS) was 66.4 months for patients treated with the Calquence combination versus 49.6 with chemoimmunotherapy alone. The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, often diagnosed at an advanced stage. An estimated 6,000 patients were diagnosed with MCL in the UK, France, Germany, Spain and Italy in 2024.

Martin Dreyling, MD, Department of Medicine, University Hospital LMU Munich, and investigator in the trial, said: “This approval provides a new first-line treatment option for patients in the EU with mantle cell lymphoma, an aggressive lymphoma with a dismal long-term outcome still today. With a progression-free survival improvement of more than 16 months for these patients, the acalabrutinib combination is a much-needed advance in this challenging disease.”

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Treatment with the Calquence combination in first-line mantle cell lymphoma demonstrated a significant improvement in progression free survival and a consistent safety profile for patients in the pivotal ECHO trial. As the first and only BTK inhibitor approved in this indication in the EU, we are proud to provide a much-needed new option to patients living with this difficult disease."

Calquence plus bendamustine and rituximab is approved in the US and several other countries in this setting based on the ECHO results. Regulatory applications are currently under review in Japan and several other countries in this indication. This approval follows the recent approval for Calquence monotherapy for the treatment of adult patients with relapsed or refractory MCL in the EU. 

ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=635) with previously untreated MCL. Patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, continuously, until disease progression or unacceptable toxicity. Additionally, all patients received six 28-day cycles of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed by rituximab maintenance for two years if patients achieved a response after induction therapy.

The primary endpoint is PFS assessed by an Independent Review Committee; other efficacy endpoints include overall survival (OS), overall response rate, duration of response and time to response. The trial was conducted in 27 countries across North and South America, Europe, Asia and Oceania.

The ECHO trial enrolled patients from May 2017 to March 2023, continuing through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for COVID-19 deaths were conducted to assess the impact of COVID-19 on the study outcome in alignment with the FDA.

Citation: Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma. Authors: Michael Wang, MD, David Salek, MD, David Belada, MD, Yuqin Song, MD, Wojciech Jurczak, MD, PhD et al. Journal of Clinical Oncology https://doi.org/10.1200/JCO-25-00690