FDA Approves First BCL2 Inhibitor for Relapsed or Refractory Mantle Cell Lymphoma

The FDA has granted accelerated approval to Beqalzi (sonrotoclax), the first BCL2 inhibitor approved for adults with relapsed or refractory mantle cell lymphoma (MCL), an aggressive form of non-Hodgkin lymphoma. The next-generation therapy is indicated for patients who have previously received at least two lines of treatment, including a Bruton's tyrosine kinase (BTK) inhibitor.

Efficacy and Safety

Efficacy was evaluated in BGB-11417-201 (NCT05471843), a single-arm, multicenter trial in 103 adults with relapsed or refractory MCL who previously received anti-CD20-based therapy and a BTK inhibitor.

Efficacy was established based on overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee (IRC) using Lugano criteria. ORR was 52% (95% CI: 42, 62), with a median time to response of 1.9 months. The median DOR was 15.8 months (95% CI: 7.4, not estimable), after an estimated median follow-up of 11.9 months.

The prescribing information includes warnings and precautions for tumor lysis syndrome (TLS), serious infections, and neutropenia. Of 115 patients with MCL evaluated for safety, serious adverse reactions occurred in 37%, most frequently from pneumonia (10%).

Recommended Dosage

The recommended sonrotoclax regimen begins with a four-week ramp-up phase to reduce TLS risk, followed by 320 mg taken orally once daily 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. FDA collaborated with the European Medicines Agency (EMA) as an official observer of this review. The applications may still be under review at the other regulatory agencies.

This application was granted priority review, breakthrough designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.