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EBMT 2025 | Using PD-1 blockade to enhance CAR T-cell efficacy in R/R LBCL
Lixia Sheng, MD, The First Affiliated Hospital of Ningbo University, Ningbo, China, comments on the potential of combining PD-1 blockade with CAR T-cell therapy in relapsed/refractory (R/R) large B-cell lymphoma (LBCL) to combat immune exhaustion and enhance CAR-T efficacy. In a Phase I trial (NCT05659628), CD19 CAR T-cells expressing IL-7 and CCL19 were combined with the anti-PD-1 antibody tislelizumab in this patient population. The approach demonstrated promising efficacy, even in patients with high PD-L1 expression at baseline. This interview took place at the 51st Annual Meeting of the EBMT in Florence, Italy.
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Transcript
Today I present our work about PD-1 blockade boosts 7×19 CAR-T efficacy in relapsed and refractory large B cell lymphoma. As we know, relapsed or refractory large B cell lymphoma remains a major clinical challenge even with the advance of CAR-T therapy. We developed 7×19 CAR T-cells which were engineered to express interleukin-7 and CCL19 to enhance the persistence and the functionality in tumor microenvironment...
Today I present our work about PD-1 blockade boosts 7×19 CAR-T efficacy in relapsed and refractory large B cell lymphoma. As we know, relapsed or refractory large B cell lymphoma remains a major clinical challenge even with the advance of CAR-T therapy. We developed 7×19 CAR T-cells which were engineered to express interleukin-7 and CCL19 to enhance the persistence and the functionality in tumor microenvironment. Furthermore, the in-vitro study revealed that the combination of these 7×19 CAR T-cells with anti-PD-1 will further boost their proliferation and cytotoxicity.
Based on these findings, we have initiated a clinical trial to assess the safety of this combination therapy. We enrolled 20 R/R LBCL patients at two centers. 18 were evaluable. Among them, 16 had unspecified diffuse large B-cell lymphoma, one had high-grade B-cell lymphoma, one had transformed follicular lymphoma.
At three months post infusion, 50% of the patients achieved complete responses and 27.8% of them had a partial response. Over time, four patients improved from PR to CR. So for the best responses. The ORR was 88.9% and the CR rate was 72.2%. Notably, the PD-L1 status significantly influenced the CR rate at three months.
We further stratified patients into two groups based on the baseline PD-L1 status. The CR rate in the higher PD-L1 group was 11.1% at three months while the CR rate in the PD-L1 low patients was 88.9%, suggesting the PD-L1 status suppresses the CAR-T activity. While after PD-1 blockade, the CR rate in the high PD-L1 group improved to 55.6%, and notably 70% of the PR patients improved to CR after PD-1 blockade, this suggesting that PD-1 blockade can enhance the CAR-T efficacy in high PD-L1 patients.
As to the survival, those PD-L1 high patients achieved comparable PFS and OS to PD-L1 low patients, indicating the potential of PD-1 blockade to enhance the CAR-T efficacy and the long-term survival in high PD-L1 patients.
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