FDA Approves Acalabrutinib Combo for Untreated Mantle Cell Lymphoma

On January 16, 2025, a significant advancement in the treatment of mantle cell lymphoma (MCL) was realized when the Food and Drug Administration (FDA) granted traditional approval for the use of acalabrutinib, known by its trade name Calquence and developed by AstraZeneca. This approval is specifically for its use in combination with bendamustine and rituximab, targeting adults diagnosed with previously untreated MCL who are not eligible for autologous hematopoietic stem cell transplantation (HSCT). Additionally, acalabrutinib received approval as a standalone therapy for adults with previously treated MCL, a condition for which it had received accelerated approval back in 2017.

The pivotal trial that underpinned the FDA’s decision is ECHO (NCT02972840), a comprehensive study that was both randomized and double-blind. It engaged 598 patients who had not previously received treatment for MCL, all aged 65 and above, and not intended for HSCT. In this study, participants were randomized in equal measure to receive either a combination of acalabrutinib with bendamustine and rituximab (BR) or a placebo paired with BR. The principal measure of efficacy was progression-free survival (PFS), assessed independently. The data revealed with a median follow-up duration of 49.8 months, that the group receiving acalabrutinib exhibited a notably extended PFS. Specifically, the acalabrutinib group had a median PFS of 66.4 months compared to 49.6 months in the placebo group, with the difference being statistically significant.

Despite its efficacy, the administration of acalabrutinib was accompanied by serious adverse reactions in 69% of the patients, with 12% encountering fatal outcomes. The common severe adverse effects included pneumonia, COVID-19, pyrexia, secondary malignancies, rash, febrile neutropenia, atrial fibrillation, sepsis, and anemia. Consequently, the dosing recommendation for acalabrutinib is 100 mg taken orally every 12 hours, continuing until the disease progresses or side effects become intolerable.

The approval process for acalabrutinib was part of Project Orbis, an initiative by the FDA Oncology Center of Excellence. This project promotes the simultaneous submission and assessment of oncology drugs by international partners. For this particular approval, the FDA worked in concert with the Therapeutic Goods Administration in Australia, Health Canada, and Switzerland's Swissmedic. The application is still under review by these agencies.

The review utilized the Assessment Aid, a voluntary tool provided by applicants to help streamline the FDA’s evaluation. It is noteworthy that this application was awarded priority review status and was designated as an orphan drug. The FDA’s expedited programs, which are detailed in their Guidance for Industry document, aim to accelerate the availability of treatments for serious health conditions.

Healthcare professionals are advised to report any serious side effects related to acalabrutinib or other medical products to the FDA's MedWatch Reporting System. This program is essential in ensuring ongoing safety and efficacy monitoring of new treatments. The FDA continues to provide resources and support to healthcare professionals, including guidance on investigational oncology products, underscoring its commitment to advancing cancer treatment.