J&J's Dual-Targeting CAR-T Shows Promise in Early Lymphoma Trial

Johnson & Johnson (J&J) has unveiled promising clinical data for its dual-targeting CAR-T therapy, potentially signaling a significant advancement in the treatment of large B-cell lymphoma. The pharmaceutical giant presented the results from a phase 1b trial at the 2025 European Hematology Association conference in Milan, Italy, showcasing impressive response rates and a manageable safety profile.

Impressive Efficacy in Early-Stage Patients

The trial, which included 22 patients treated with the recommended phase 2 dose, demonstrated remarkable efficacy, particularly in those who had received only one prior line of treatment. Among these ten patients, J&J reported a 100% objective response rate (ORR), with eight patients achieving a complete response, meaning all signs of cancer were undetectable.

For the twelve patients who had undergone two or more previous therapies, the results remained highly encouraging, with a 92% ORR and a 75% complete response rate. These data suggest that J&J's CAR-T therapy could potentially offer a more effective treatment option for patients with relapsed or refractory large B-cell lymphoma.

Safety Profile and Technical Aspects

The safety arm of the trial, comprising 25 patients, revealed that 84% experienced grade 3 or 4 treatment-related adverse events, with 28% facing serious side effects. Notably, there were no cases of grade 3 or 4 cytokine release syndrome, a common concern with CAR-T therapies. One patient developed grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS), while another with central nervous system lymphoma experienced grade 3 ICANS.

J&J's CAR-T therapy, known as JNJ-4496, targets both CD19 and CD20 cell surface proteins, which are commonly expressed by cancerous B cells. This dual-targeting approach aims to improve upon the efficacy of existing single-antigen-targeting CD19 CAR-T therapies, which currently achieve long-term remissions in only about 40% of patients.

Strategic Implications for J&J and the CAR-T Landscape

The development of JNJ-4496 marks J&J's re-entry into the CAR-T field following the 2022 approval of Carvykti, developed in partnership with Legend Biotech. The company acquired the rights to JNJ-4496 through a $245 million upfront payment to AbelZeta (formerly Cellular Biomedicine Group) in 2023, securing ex-China rights to the therapy.

This move comes at a time when the cell therapy landscape is experiencing significant challenges, with several biotechs facing setbacks or shutdowns due to high costs and clinical struggles. J&J's progress with JNJ-4496 could potentially reinvigorate interest in the field and offer new hope for patients with aggressive lymphomas.