FDA Approves AstraZeneca’s Calquence for Previously Untreated Mantle Cell Lymphoma

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The FDA has approved AstraZeneca’s Calquence (acalabrutinib), in combination with bendamustine and rituximab, for the first-line treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation. The approval followed the FDA granting the application with Priority Review status and with support from the Phase III ECHO trial, which demonstrated that the Calquence regimen significantly reduced the risk of disease progression or death compared to standard chemoimmunotherapy.¹

"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 today’s approval underscoring the transformative potential of this regimen as a first-line treatment for older patients with mantle cell lymphoma,” said principal trial investigator Michael Wang, MD, Puddin Clarke endowed professor, director, mantle cell lymphoma program of excellence, in a press release.

The randomized, double-blind, placebo-controlled, multi-center ECHO trial evaluated the efficacy and safety of Calquence plus bendamustine and rituximab compared to standard of care chemotherapy in adults over 65 years of age. During the trial, patients were randomly assigned in a 1:1 ratio to receive Calquence or placebo twice a day until disease progression or unacceptable toxicity. Patients also received six 28-day cycles of bendamustine during the first two days of each cycle as well as rituximab on the first day of each cycle, followed by rituximab maintenance for two years if there was a response from induction therapy. The primary endpoint of the study was progression-free survival (PFS) assessed by an Independent Review Committee, with secondary endpoints that included overall survival, overall response rate, duration of response, and time to response.

Results found that Calquence demonstrated a 27% reduction in the risk of disease progression or death compared to standard of care chemotherapy. Additionally, the median PFS was 66.4 months for patients treated with the combination compared to 49.6 months for chemotherapy alone.

Common adverse events (AEs) included rash; COVID-19; fatigue; headache; upper respiratory tract infection; pyrexia; cough; vomiting; constipation; hemorrhage; edema; secondary primary malignancy; dizziness; arthralgia; and dyspnea. Serious AEs were reported in 69% of patients who received the combination, with 12% experiencing fatal AEs. AEs led to discontinuation in 43% of patients and dosage interruptions in 74%.¹

"With today’s 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,” said Dave Fredrickson, EVP, oncology business unit, AstraZeneca, in the press release.

According to UpToDate, MCL accounts for 3% to 7% of all non-Hodgkin lymphomas in the United States and Europe. Median diagnosis is 68 years of age and an estimated three-quarters of patients are male. Additionally, white individuals are more commonly affected than Black individuals.²

"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,” said Meghan Gutierrez, CEO, Lymphoma Research Foundation, in the press release.

References

1. CALQUENCE® (acalabrutinib) plus chemoimmunotherapy approved in the US for patients with previously untreated mantle cell lymphoma. Yahoo!finance. January 17, 2025. Accessed January 17, 2025. https://finance.yahoo.com/news/calquence-acalabrutinib-plus-chemoimmunotherapy-approved-120000864.html

2. Mantle cell lymphoma: Epidemiology, pathobiology, clinical manifestations, diagnosis, and prognosis. UpToDate. Accessed January 17, 2025. https://www.uptodate.com/contents/mantle-cell-lymphoma-epidemiology-pathobiology-clinical-manifestations-diagnosis-and-prognosis#:~:text=Mantle%20cell%20lymphoma%20(MCL)%20accounts,as%20frequently%20as%20Black%20individuals.