FDA Approves Acalabrutinib With Bendamustine and Rituximab for Frontline MCL

The FDA has approved acalabrutinib with bendamustine and rituximab for the treatment of mantle cell lymphoma (MCL) in the frontline setting for adult patients ineligible for hematopoietic stem cell transplantation.¹

Acalabrutinib was previously granted priority review in October 2024 based on results from the phase 3 ECHO trial, in which acalabrutinib combined with bendamustine and rituximab reduced the risk of disease progression or death by 27% compared with standard-of-care chemoimmunotherapy (hazard ratio, 0.73; 95% CI, 0.57-0.94; P=.016). The median progression-free survival (PFS) was 66.4 months for the acalabrutinib combination and 49.6 months for standard-of-care chemoimmunotherapy. Overall survival also showed a favorable trend with acalabrutinib.²

Additional efficacy and safety results of the ECHO trial were presented at the 66th American Society of Hematology Annual Meeting & Exposition by Martin Dreyling, MD, of Klinikum der Universitaet Munchen in Germany. Data showed that acalabrutinib plus bendamustine and rituximab significantly improved PFS compared with placebo plus bendamustine and rituximab for patients with high-risk characteristics.³

Among those with measurable residual disease (MRD) positivity at the end of induction, 37.5% in the acalabrutinib combination arm and 20% in the placebo arm had achieved MRD negativity during maintenance. Similar rates of treatment-emergent adverse events were reported in each arm.³

References

1. FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. US Food and Drug Administration. 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
2. Calquence plus chemoimmunotherapy reduced the risk of disease progression or death by 27% vs. standard of care in patients with untreated mantle cell lymphoma in ECHO Phase III trial. AstraZeneca. June 16, 2024. Accessed January 10, 2025. https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percent.html
3. Dreyling M, Mayer J, Song Y, et al. High-risk subgroups and MRD: an updated analysis of the phase 3 ECHO Trial of acalabrutinib with bendamustine/rituximab in previously untreated mantle cell lymphoma. Abstract #1626. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.