FDA Approves Acalabrutinib With Bendamustine and Rituximab for Patients With Previously Untreated MCL

On January 16, 2025 the US Food and Drug Administration (FDA) approved acalabrutinib with bendamustine and rituximab for the treatment of patients with previously untreated mantle cell lymphoma (MCL) ineligible for autologous hematopoietic stem cell transplantation (HSCT).

Additionally, the FDA the granted traditional approval to acalabrutinib as a single agent treatment for adults with previously treated MCL, as acalabrutinib treatment was previously granted accelerated approval for this particular indication in 2017.

This latest approval was based on efficacy and safety results from the ECHO trial, a randomized, double-blind, multicenter trial conducted with 598 patients with untreated MCL who were 65 years of age or older and not planned to receive HSCT. Patients were randomized 1 to 1 to receive acalabrutinib plus bendamustine and rituximab (acalabrutinib plus BR) or a placebo plus BR.

Efficacy was based on progression-free survival (PFS), as assessed by an independent review committee. With a median follow-up of 49.8 months, PFS was statistically significantly longer in the acalabrutinib arm (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.57 to 0.94, p-value = 0.016). The median PFS was 66.4 months (95% CI, 55.1 to not estimable) in the acalabrutinib plus BR arm and 49.6 months (95% CI, 36.0 to 64.1) in the placebo plus BR arm.

As for adverse events, serious adverse reactions occurred in 69% of patients with acalabrutinib plus BR, and fatal adverse reactions occurred in 12%. The serious adverse reactions reported in ≥2% of patients were pneumonia, COVID-19, pyrexia, second primary malignancy, rash, febrile neutropenia, atrial fibrillation, sepsis, and anemia.

The approval noted that the recommended acalabrutinib dose is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity.

Source:

FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. Press Release. The US Food and Drug Administration. Published online January 16, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-acalabrutinib-bendamustine-and-rituximab-previously-untreated-mantle-cell-lymphoma