BMS’s CD19 CAR-T Breyanzi breaks ground with indication nod for MZL

Bristol Myers Squibb announced US FDA indication approval for Breyanzi (lisocabtagene maraleucel; liso-cel) as a treatment for adult patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL) after at least two prior systemic therapies. The decision marks the first approval of a CAR-T therapy for MZL, expanding Breyanzi’s reach to a fifth distinct B-cell malignancy.

Breyanzi is a CD19-targeted CAR-T originally developed by Juno Therapeutics, acquired by Celgene in 2018, and subsequently by BMS in 2019. The therapy was first approved for R/R large B-cell lymphoma in 2021, and the new indication further strengthens BMS’s cell therapy portfolio.

Strong efficacy in heavily pretreated MZL

Approval was supported by the MZL cohort of the Phase 2 TRANSCEND FL-MZL trial (NCT04245839), a multicentre, single-arm study in patients with R/R disease. Among 66 efficacy-evaluable patients: • ORR: 84.4% (95% CI: 74.4–91.7) • CRR: 55.8% (95% CI: 44.1–67.2) • Median DOR: Not reached (95% CI: 25.6 months–NR), indicating sustained remissions

Breyanzi is given as a one-time infusion following lymphodepleting chemotherapy. Safety data in MZL showed: • CRS: 76% of patients (Grade ≥3 in 4–5%) • Neurologic events: Observed but with rare severe cases

Dr. M. Lia Palomba of Memorial Sloan Kettering Cancer Center noted that while frontline therapy for MZL is effective for many, repeated relapses are frequent. The approval “redefines the treatment landscape,” offering deep and durable responses in advanced lines.

What this approval means

MZL is an indolent yet recurrent B-cell lymphoma comprising extranodal, nodal, and splenic subtypes. Standard regimens typically focus on anti-CD20 antibodies such as rituximab, alone or with chemotherapy, and often fail over time due to resistance or intolerance.

Breyanzi introduces a new therapeutic modality with high response rates and potential long-term remission, positioning it as a transformative option in late-line MZL. With this approval, Breyanzi becomes the only CD19 CAR-T with five US indications, giving BMS the broadest CAR-T footprint in the CD19 space.

Competitive landscape

MZL is an active development area for dozens of companies pursuing novel mechanisms, with Breyanzi competing with: • Zanubrutinib (BeiGene): A BTK inhibitor approved for MZL in 2021 based on the MAGNOLIA study. • Glofitamab (Roche): A CD20×CD3 bispecific antibody, tested with obinutuzumab in indolent lymphomas including MZL. • Copanlisib (Bayer): A PI3K inhibitor studied in combination with rituximab for MZL. • Venetoclax (AbbVie/Roche): A BCL2 inhibitor in frontline trials with rituximab for MZL.

The approval of Breyanzi may accelerate interest in cell therapies for indolent lymphomas and further shift the standard of care toward personalised, immune-based treatments.