A new BCL-2 inhibitor will be made available in the relapsed mantle cell lymphoma (MCL) space after the US FDA granted accelerated approval to Beqalzi (sonrotoclax), developed by BeOne Medicines USA, Inc., (Nasdaq: ONC). Specifically, the indication covers adults with relapsed or refractory MCL who have received at least two prior lines of systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor. The approval adds a second mechanistic class to a post-BTKi setting that has historically offered limited options.

The accelerated approval covers adults with relapsed or refractory MCL after at least two prior systemic therapies, including a BTK inhibitor. To manage tumor lysis syndrome (TLS) risk, the recommended regimen begins with a four-week ramp-up phase before reaching the maintenance dose of 320 mg orally once daily, continued until disease progression or unacceptable toxicity. The prescribing information carries warnings for TLS, serious infections, and neutropenia. The review was conducted under Project Orbis, a US FDA Oncology Center of Excellence initiative enabling concurrent international submissions; the European Medicines Agency participated as an official observer, with its review ongoing. The application received priority review designation.

Efficacy was evaluated in BGB-11417-201 (NCT05471843), a single-arm, multicenter Phase II trial enrolling 103 adults with relapsed or refractory MCL who had previously received anti-CD20-based therapy and a BTK inhibitor. The primary endpoints were overall response rate (ORR) and duration of response (DOR), assessed by an independent review committee using Lugano criteria. ORR was 52% (95% CI: 42–62), with a median time to response of 1.9 months; median DOR was 15.8 months (95% CI: 7.4, not estimable) at a median follow-up of 11.9 months. Serious adverse reactions occurred in 37% of the 115 patients evaluated for safety, with pneumonia the most frequent at 10%.

Beqalzi joins a post-BTKi MCL landscape that includes pirtobrutinib (Jaypirca, Eli Lilly), a non-covalent BTK inhibitor approved in 2023 for the same line of therapy, and lisocabtagene maraleucel (Breyanzi, Bristol Myers Squibb), a CD19-directed CAR-T therapy approved for relapsed or refractory MCL after prior BTK inhibitor exposure. Sonrotoclax’s BCL-2 inhibition mechanism offers a pharmacologically distinct approach from both, potentially informing sequencing decisions in a population that has exhausted BTK inhibitor options.

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