AstraZeneca PLC announced that Positive high-level results from an interim analysis of the ECHO Phase III trial showed AstraZeneca's Calquence (acalabrutinib) in combination with standard-of-care chemoimmunotherapy, bendamustine and rituximab, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus standard of care in previously untreated adult patients with mantle cell lymphoma (MCL). A trend was observed in favour of Calquence plus chemoimmunotherapy for the secondary endpoint of overall survival (OS). The OS data were not mature at the time of this analysis and the trial will continue to assess OS.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed as a late-stage disease, resulting when B- lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone. It is estimated that there are more than 27,500 patients diagnosed with MCL worldwide. The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. As part of an extensive clinical development programme, AstraZeneca is currently evaluating Calquence alone and in combination for the treatment of multiple B-cell blood cancers, including chronic lymphocytic leukaemia (CLL), MCL, and diffuse large B-cell lymphoma. Calquence has been used to treat more than 80,000 patients worldwide and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan and China for relapsed or refractory CLL and SLL.

Calquence is also approved in the US, China and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU. Mantle cell lymphoma MCL is an uncommon subtype of B-cell non-Hodgkin lymphoma.

MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it is estimated that approximately 4,000 new cases of MCL are diagnosed each year. While MCL patients initially respond to treatment, patients do tend to relapse. ECHO 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 standard of care chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=598) with previously untreated MCL.7 In the experimental arms, patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, on 28 day treatment cycles, plus bendamustine on days 1 and 2 and rituximab on day 1. After six cycles of Calquence or placebo in combination with bendamustine and rituximab, patients receive Calquence or placebo plus maintenance rituximab for two years and then either Calquence or placebo only until disease progression.

The primary endpoint is PFS and key secondary endpoints include OS, overall response rate (ORR), duration of response (DoR) and time to response (TTR).7 The trial includes 27 countries across North and South America, Europe, Asia and Oceania. The ECHO trial was conducted from 2017 to 2023 continuing through the COVID-19 pandemic. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.