Acalabrutinib Plus Bendamustine and Rituximab Receives FDA Approval in MCL

• The FDA has approved acalabrutinib (Calquence) plus bendamustine and rituximab (Rituxan; BR) for adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).
• The supplemental new drug application was granted priority review in October 2024.
• Findings from the phase 3 ECHO trial (NCT02972840) support the approval.

The FDA granted approval to acalabrutinib plus BR for the treatment of adult patients with previously untreated MCL who are ineligible for autologous HSCT.¹

Findings from the ECHO trial that were presented at the 2024 European Hematology Association Hybrid Congress support this approval. Here, acalabrutinib plus BR reduced the risk of disease progression or death by 27% vs BR alone (HR, 0.73; 95% CI, 0.57-0.94; P =.016). The addition of acalabrutinib also led to nearly 1.5 years of additional median progression-free survival (PFS), with a median PFS of 66.4 months with acalabrutinib plus BR and 49.6 months with BR alone.^2,3

There was a positive overall survival (OS) trend observed with acalabrutinib plus BR vs BR alone (HR, 0.86; 95% CI, 0.65-1.13; P =.2743); however, most patients in the BR arm who required a subsequent therapy went on to receive a BTK inhibitor, often acalabrutinib. OS data will continue to be assessed as a key secondary end point.

Background of the Phase 3 ECHO Trial

ECHO randomized patients 1:1 to receive acalabrutinib plus BR (n = 299) or placebo plus BR (n = 299). Acalabrutinib or placebo were administered twice daily orally, with bendamustine administered on days 1 and 2 and rituximab on day 1 for 28-day cycles.^3,4

The study’s primary end point was PFS per independent review committee, and secondary end points included investigator-assessed PFS, overall response rate, OS, duration of response, and time to response.

Patients were eligible for study participation if they had pathologically confirmed MCL with documentation of a chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers, had not received prior systemic anticancer therapies, were 65 years old or younger, and had an ECOG performance status of 2 or lower. Those with significant cardiovascular disease, malabsorption syndrome, or uncontrolled active infection were not eligible for participation.

Acalabrutinib previously received accelerated approval from the FDA for the treatment of adult patients with MCL following at least 1 prior therapy.⁵ This accelerated approval is contingent on the results of a confirmatory trial.

REFERENCES:

1. FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. FDA. January 16, 2024. Accessed January 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-bendamustine-and-rituximab-previously-untreated-mantle-cell-lymphoma

2. CALQUENCE® (acalabrutinib) granted priority review in the US for patients with untreated mantle cell lymphoma. News release. AstraZeneca. October 3, 2024. Accessed October 29, 2024. https://tinyurl.com/27pn2twc

3. Wang ML, Mayer J, Belada D, et al. Acalabrutinib plus bendamustine and rituximab in untreated mantle cell lymphoma: results from the phase 3, double-blind, placebo-controlled ECHO trial. Abstract presented at: European Hematology Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain. Abstract LBA3439.

4. A study of BR alone versus in combination with acalabrutinib in subjects with previously untreated MCL. ClinicalTrials.gov. Updated June 18, 2024. Accessed October 29, 2024. https://clinicaltrials.gov/study/NCT02972840

5. FDA grants accelerated approval to acalabrutinib for mantle cell lymphoma. News release. FDA. October 31, 2017. Accessed October 29, 2024. https://tinyurl.com/4t7yf7cf