USFDA approves AstraZeneca Calquence, bendamustine, rituximab combo for previously untreated mantle cell lymphoma

The approval was granted after securing Priority Review. It was based on results from the ECHO Phase III trial which were presented at the European Hematology Association 2024 Congress.

Read also: AstraZeneca Calquence granted priority review by USFDA for previously untreated mantle cell lymphoma

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed at an advanced stage. It is estimated that there are more than 21,000 patients diagnosed with MCL in the US, UK, France, Germany, Spain, Italy, Japan and China.

Michael Wang, MD, Puddin Clarke Endowed Professor, Director of Mantle Cell Lymphoma Program of Excellence and principal investigator in the trial, said, "Managing this aggressive cancer requires maximizing efficacy while maintaining tolerability, especially for elderly patients. Results from the pivotal ECHO trial highlight the promise of the acalabrutinib combination in defining a new standard of care, with this approval underscoring the transformative potential of this regimen as a first-line treatment for older patients with mantle cell lymphoma.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said, “With the approval, CALQUENCE provides a critical new treatment option to mantle cell lymphoma patients in the US, with CALQUENCE proven to deliver nearly one and a half years of additional time without disease progression. This approval brings a new and effective treatment option to those living with this disease and further reinforces our belief in CALQUENCE as a backbone therapy across multiple blood cancers.”

Meghan Gutierrez, Chief Executive Officer, Lymphoma Research Foundation, said, “New treatment options have long been needed in the first-line treatment of mantle cell lymphoma in the US. Patients with this rare and often aggressive cancer can experience severe symptoms by the time they are diagnosed - having an effective therapy that can significantly improve outcomes for patients early in the treatment process is a much-needed advancement.”

Results from the ECHO trial showed 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 PFS was 66.4 months for patients treated with the CALQUENCE combination versus 49.6 months with chemoimmunotherapy alone.

This approval additionally converts CALQUENCE’s accelerated approval to a full approval for adult patients with MCL treated with at least one prior therapy, as granted by the FDA in October 2017.

The ECHO trial enrolled patients throughout the COVID-19 pandemic. After censoring for COVID-19 deaths, PFS was further improved in both arms, with the CALQUENCE combination reducing the risk of disease progression or death by 36% (HR 0.64; 95% CI 0.48-0.84). Although OS data were not mature at the time of the analysis, when censored for COVID-19, a favorable trend was seen for OS (HR 0.75; 95% CI 0.53-1.04), despite 69% of patients in the chemoimmunotherapy arm receiving treatment with a BTK inhibitor on relapse or disease progression.

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

The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, CALQUENCE plus chemoimmunotherapy is also under review by regulatory authorities in Australia, Canada, and Switzerland for the same indication. Regulatory applications are also under review in the EU, Japan, and other countries based on the ECHO results.

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated in combination with bendamustine and rituximab (BR) for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT), as monotherapy for the treatment of adult patients with MCL who have received at least one prior therapy, and for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).