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December 8, 2025BloodOpen Access

Immune exhaustion limits CD19 CAR-T efficacy in Richter's transformation

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Authors

SHSean HaneyDMDouglas MarachionMHMohammad Hussaini

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Overview

Retrospective analysis reveals overall response rates in chronic lymphocytic leukemia patients with CD19 CAR-T, suggesting implications for tumor microenvironment.

Key Points

  • This study evaluates the outcomes and immune factors associated with CD19 CAR-T therapy in Richter's transformation.
  • Retrospective analysis of 15 patients with Richter's transformation and 19 with de novo DLBCL treated with CD19 CAR-T.
  • Pre-infusion PBMCs analyzed through multiparametric flow cytometry.
  • RNA expression from tumor biopsies assessed using NanoString transcriptomic profiling.
  • Overall response rates of 80% at day 30 and 47% at 3 months in Richter's transformation patients.
  • Higher frequencies of exhausted T cells observed in Richter's transformation patients compared to de novo DLBCL.
  • Increased ENTPD1 and DUSP2 expression linked to poor CAR-T durability in Richter's transformation.

Cite This Study

Haney et al. (2025) studied this question.

synapsesocial.com/papers/693624dd4fa91c937236d279https://doi.org/10.1182/blood-2025-1791
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Multi-centre real-world outcome of patients with Richter transformation receiving CD19-directed commercial CAR T-cell therapy in Australia.2025
  2. 2Efficacy and safety of chimeric antigen receptor (CAR) T-cell therapy in richter transformation: A systematic review and meta-analysis2025
  3. 3Immune landscape characterization of relapsed/refractory B-cell lymphoma patients treated with CD19 CAR-T cell therapy2025
  4. 4Timed PD-1 blockade synergizes with IL-7/CCL19 armoring to reverse CAR-T exhaustion in PD-L1-high large B-cell lymphoma2025
  5. 5Pre-existing cytotoxic capacity of CD8+ and CD4+ T cells is a hallmark of richter transformation and favors response to anti-PD-1 therapy2025