AstraZeneca’s CALQUENCE (acalabrutinib) in combination with bendamustine and rituximab was approved in the US for the treatment of adult patients with previously untreated mantle cell lymphoma.
The approval was granted by the Food and Drug Administration (FDA) after securing Priority Review. It was based on results from the ECHO Phase III trial, which had been presented at the European Hematology Association 2024 Congress.
MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed at an advanced stage. It was estimated that there were more than 21,000 patients diagnosed with MCL in the US, UK, France, Germany, Spain, Italy, Japan, and China.
About The ECHO trial
The ECHO trial demonstrated that CALQUENCE (acalabrutinib) in combination with bendamustine and rituximab significantly reduced the risk of disease progression or death by 27% compared to standard-of-care chemoimmunotherapy for patients with mantle cell lymphoma (MCL). The hazard ratio (HR) was 0.73 (95% confidence interval [CI] 0.57-0.94; p=0.016), and median progression-free survival (PFS) was 66.4 months for patients treated with the CALQUENCE combination, compared to 49.6 months for those on chemoimmunotherapy alone.
This approval also converted CALQUENCE’s accelerated approval (granted by the FDA in October 2017) to a full approval for adult patients with MCL who had received at least one prior therapy.
The ECHO trial had progression-free survival (PFS) as its primary endpoint, assessed by an Independent Review Committee. Other key efficacy endpoints included overall survival (OS), overall response rate (ORR), duration of response (DoR), and time to response (TTR). The trial was conducted in 27 countries across North and South America, Europe, Asia, and Oceania, enrolling patients from May 2017 to March 2023.
The ECHO trial enrolled patients throughout the COVID-19 pandemic, and after censoring for COVID-19-related deaths, PFS was further improved in both treatment arms. The CALQUENCE combination reduced the risk of progression or death by 36% (HR 0.64; 95% CI 0.48-0.84). Though overall survival (OS) data were not mature at the time of analysis, there was a favorable trend for OS when censored for COVID-19 (HR 0.75; 95% CI 0.53-1.04). Notably, 69% of patients in the chemoimmunotherapy arm received treatment with a BTK inhibitor upon relapse or progression.
The safety profile of CALQUENCE was consistent with previous findings, and no new safety concerns were identified. The US regulatory submission was reviewed under Project Orbis, a program that facilitates concurrent review of oncology medicines by international regulatory authorities. CALQUENCE plus chemoimmunotherapy is currently under review in Australia, Canada, Switzerland, and other countries, based on the results of the ECHO trial.
About CALQUENCE (acalabrutinib)
CALQUENCE (acalabrutinib) is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with various hematologic malignancies. It is used in combination with bendamustine and rituximab (BR) for the treatment of previously untreated mantle cell lymphoma (MCL) in patients who are ineligible for autologous hematopoietic stem cell transplantation (HSCT). It is also approved as monotherapy for adult patients with MCL who have received at least one prior therapy. Additionally, CALQUENCE is indicated for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in adult patients.
Important Safety Information
CALQUENCE has been associated with serious and opportunistic infections in patients with hematologic malignancies. Fatal and serious infections, including bacterial, viral, and fungal infections, have occurred. In clinical trials, 32% of 1,764 patients treated with CALQUENCE experienced serious or Grade 3 or higher infections, most frequently respiratory tract infections (19%, including pneumonia in 9%). These infections often occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 2.7% of patients.
Opportunistic infections linked to CALQUENCE treatment have included conditions like hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). For patients at higher risk of such infections, prophylactic treatment should be considered. It is essential to monitor patients for signs and symptoms of infection and provide prompt treatment as necessary.