FDA Approves Acalabrutinib With Bendamustine, Rituximab For Patients With Previously Untreated Mantle Cell Lymphoma

Key Takeaways

Acalabrutinib, combined with bendamustine and rituximab, received FDA approval for untreated mantle cell lymphoma patients ineligible for HSCT, based on the ECHO trial results.
The ECHO trial showed significant improvements in progression-free survival and a favorable trend in overall survival, reducing disease progression risk by 27% compared to standard care.
The safety profile of the acalabrutinib combination was consistent with previous studies, with no new safety signals observed.
This approval provides a new first-line treatment option for older patients with mantle cell lymphoma, addressing a critical need for effective therapies.

Acalabrutinib with bendamustine and rituximab shows efficacy in patients with untreated mantel cell lymphoma by increasing progression-free survival in the ECHO trial.

The FDA granted traditional regulatory approval to acalabrutinib (Calquence; AstraZeneca), in combination with bendamustine and rituximab, for adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible to receive autologous hematopoietic stem cell transplantation (HSCT), according news releases from the FDA and AstraZeneca.^1,2

Mantle cell lymphoma can be especially serious for those at older age or who are immunocompromised, necessitating reliable treatment options. | Image Credit: © Adobe Contributor | stock.adobe.com

This approval is based on the positive results of the phase 3 ECHO clinical trial (NCT02972840), which had data showcased at the European Hematology Association 2024 Congress earlier last year. In ECHO, acalabrutinib in combination with bendamustine and rituximab led to clinically meaningful and statistically significant improvements in progression-free survival (PFS), alongside a favorable trend in overall survival (OS) compared with standard chemotherapy.^3,4

The drug combination reduced the risk of disease progression or death by 27% compared with patients receiving standard-of-care (HR: 0.73; 95% CI, 0.57-0.94; P = .016), according to AstraZeneca. For patients treated with the acalabrutinib combination, median PFS was 66.4 compared with 49.6 months for patients receiving chemotherapy alone, indicating the combination’s strong therapeutic potential and providing a thorough set of efficacy data backing its approval.²

Because the trial enrolled patients throughout the COVID-19 pandemic, study investigators censored data for COVID-19 deaths. Upon this, PFS was further improved in both arms; acalabrutinib combination therapy reduced the risk of death or disease progression by 36% (HR: 0.64; 95% CI, 0.48-0.84). Data regarding OS were not mature at the point of analysis, but the investigators observed a favorable OS trend when censored for COVID-19 (HR: 0.75; 95% CI, 0.53-1.04).²

About the Trial

Trial Name: A Study of BR Alone Versus in Combination With Acalabrutinib in Subjects With Previously Untreated MCL

ClinicalTrials.gov ID: NCT02972840

Sponsor: Acerta Pharma BV

Completion Date: October 28, 2025

In 2017, the FDA granted accelerated approval to acalabrutinib alone to treat patients with MCL who had received at least 1 prior therapy. The new FDA action now converts this accelerated approval into a full, traditional approval, providing patients in this population a new option for treatment and giving pharmacists a broader portfolio of potential medications to use for managing their patients.^2,5

“Managing this aggressive cancer requires maximizing efficacy while maintaining tolerability, especially for elderly patients,” Michael Wang, MD, principal investigator in the ECHO trial, said in the news release from AstraZeneca. “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.”²

A next-generation, selective Bruton tyrosine kinase (BTK) inhibitor, acalabrutinib covalently binds to BTK to inhibit signaling activity. Through BTK signaling, pathways are activated that lead to the proliferation, trafficking, chemotaxis, and adhesion of cancerous B-cells. Acalabrutinib has a series of regulatory approvals under its belt already, including being approved for the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) in the US.^2,3

The observed safety profile of the acalabrutinib combination was reported to be like those of previous studies. Serious adverse events (AEs) were observed in 69% of patients with acalabrutinib plus bendamustine and rituximab. Some of these serious AEs include pneumonia, COVID-19, febrile neutropenia, and anemia. Pharmacists and other members of the patient care team play an important role in monitoring for serious AEs and treating them appropriately as they arise.^1,2

Importantly, there were no new safety signals observed in ECHO, according to AstraZeneca.²

“New treatment options have long been needed in the first-line treatment of mantle cell lymphoma in the US,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in the news release. “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.”²

REFERENCES

1. FDA. FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. News Release. Released January 16, 2025. Accessed January 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-bendamustine-and-rituximab-previously-untreated-mantle-cell-lymphoma?utm_medium=email&utm_source=govdelivery

2. AstraZeneca. Calquence plus chemoimmunotherapy approved in the US for patients with previously untreated mantle cell lymphoma. News Release. Released January 17, 2025. Accessed January 17, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/calquence-combination-approved-in-us-for-1l-mcl.html

3. McGovern G. Acalabrutinib combination treatment improves progression-free survival in patients with previously untreated MCL. Pharmacy Times. Published June 19, 2024. Accessed January 17, 2025.

4. ClinicalTrials.gov. A study of BR alone versus in combination with acalabrutinib in subjects with previously untreated MCL. National Library of Medicine. Last Updated November 29, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT02972840

5. FDA. FDA grants accelerated approval to acalabrutinib for mantle cell lymphoma. News Release. Released October 31, 2017. Accessed January 17, 2025. https://wayback.archive-it.org/7993/20201222070214/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-acalabrutinib-mantle-cell-lymphoma