New Approvals for Acalabrutinib in Mantle Cell Lymphoma
Acalabrutinib was granted traditional approval as a monotherapy for previously treated MCL and as part of a combination for untreated MCL.
The U.S. Food and Drug Administration (FDA) has granted traditional approval to acalabrutinib (Calquence), in combination with bendamustine and rituximab, for the treatment of adult patients with mantle cell lymphoma (MCL) who had not previously received treatment for their disease.
The FDA concurrently granted traditional approval to acalabrutinib as a single-agent therapy for adult patients with previously treated MCL, an indication that had previously received an accelerated approval.
Acalabrutinib is a targeted therapy that blocks the activity of Bruton’s tyrosine kinase (BTK), a protein expressed on the surface of B cells, the type of cell MCL develops from. By blocking BTK, acalabrutinib suppresses signals that help MCL cells proliferate.
Rituximab is an antibody that binds to CD20, another protein expressed on the surface of B cells. When rituximab binds to CD20-expressing cells, including MCL cells, it attracts the immune system to attack them. Bendamustine is a type of chemotherapy.
This is the first approval for acalabrutinib in patients with previously untreated MCL.
The approval was based on results from the randomized, double-blind, placebo-controlled, multicenter phase III ECHO clinical trial. Researchers enrolled 598 patients with MCL who had not received previous treatments for their disease, were aged 65 or older, and did not intend to receive a stem cell transplant. Patients were randomly assigned (1:1) to receive acalabrutinib plus bendamustine and rituximab (acalabrutinib arm) or placebo plus bendamustine and rituximab (placebo arm).
Patients in the acalabrutinib arm survived without disease progression for a median of 66.4 months, and patients in the placebo arm survived without disease progression for a median of 49.6 months. Patients in the acalabrutinib arm were 27% less likely to experience disease progression or death than those in the placebo arm.
The prescribing information for rituximab contains a boxed warning for fatal infusion-related reactions, severe mucocutaneous reactions, hepatitis B virus reactivation, and progressive multifocal leukoencephalopathy.
The recommended dose of acalabrutinib is 100 mg taken twice a day until disease progression or unacceptable toxicity. The recommended dose of rituximab is 375 mg/m2 of body surface area. The recommended dose of bendamustine is 120 mg/m2 of body surface area on days one and two of each 21-day cycle, for up to eight cycles.
Mantle cell lymphoma is a type of non-Hodgkin lymphoma that arises from immune cells called B cells. Approximately 3% to 10% of non-Hodgkin lymphomas are MCL. According to federal statistics, it was estimated that 80,620 individuals would be diagnosed with non-Hodgkin lymphoma and 20,140 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on January 16, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.
