On January 16, 2025, the Food and Drug Administration granted traditional approval to acalabrutinib with bendamustine and rituximab for adults with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT).

FDA also granted traditional approval to acalabrutinib as a single agent for adults with previously treated MCL. Acalabrutinib receivedExternal Link Disclaimer accelerated approval for this indication in 2017.

Full prescribing information for acalabrutinib will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in ECHO (NCT02972840), a randomized, double-blind, placebo controlled, multicenter trial in 598 patients with untreated MCL who were ≥65 years of age and not intended to receive HSCT. Patients were randomized (1:1) to receive acalabrutinib plus bendamustine and rituximab (acalabrutinib plus BR) or 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 0.73 [95% CI: 0.57, 0.94], p-value 0.016). The median PFS was 66.4 months (95% CI: 55.1, not estimable) in the acalabrutinib plus BR arm and 49.6 months (95% CI: 36.0, 64.1) in the placebo plus BR arm.

Serious adverse reactions occurred in 69% of patients with acalabrutinib plus BR, and fatal adverse reactions occurred in 12%. 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 recommended acalabrutinib dose is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Source: FDA