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ESMO 2025 Bispecific CAR T-cell therapy shows high response rate in R/R DLBCL

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MedNet.nl: A bispecific CAR T-cell therapy targeting both CD19 and CD22 leads to a high response rate in patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). This is evident from a Chinese phase 2 study.

The introduction of anti-CD19 CAR T-cell therapy has significantly improved the treatment outcomes of R/R DLBCL. Nevertheless, there is a substantial group of patients in whom the treatment has no long-term effect, for example due to antigen loss or resistance. The hope is that a lasting treatment effect will be achieved in more patients when CAR T-cell therapy targets multiple antigens.

The researchers produced CAR-T cells targeting CD19 and CD22, naming the product CAR2219. This drug was tested in 31 patients with R/R DLBCL who had received a median of three previous treatments. The primary endpoint was response (ORR) 3 months after infusion of the CAR-T cells. Bridging therapy prior to infusion was permitted, and patients who responded to CAR2219 received maintenance treatment with a PD-1 inhibitor.

After a median follow-up of 4.2 months, the ORR was 100%, with a complete response in 67.7% and a partial response in 32.3%. Median progression-free survival (PFS) and overall survival (OS) had not yet been reached. The 6-month PFS and OS were 83.0% and 87.1%, respectively. At the time of analysis, 93.5% of participants were still alive.

The most common hematologic adverse events were neutropenia (93%), thrombocytopenia (77%), and anemia (71%). Cytokine release syndrome (CRS) occurred in 74% of patients, with no grade ≥3 adverse events. Immune effector cell-associated neurotoxicity syndrome (ICANS) was also relatively rare (6%; one grade 3 event).

The researchers suggest that the role of maintenance treatment with a PD-1 inhibitor should be further investigated.

Wang L, et al. CD19/CD22 bispecific CAR-T cell therapy for relapsed/refractory large B-cell lymphoma: a prospective, single-arm, single-center, phase II clinical trial. ESMO 2025, abstract 1240O.

This article was originally published in Dutch on MedNet.nl

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Woman receiving an intravenous infusion/© FatCamera / Getty Images / iStock (symbolic image with model), Erica Mayer/© Springer Medicine, Christof Vulsteke/© Springer Medicine, Jeanne Tie/© Springer Medicine, DNA testing of blood - conceptual/© blindturtle / stock.adobe.com