Patient-Derived Lymphoma Spheroids Reveal Predictive Markers of Glofitamab Resistance in Relapsed/Refractory B-NHL - PubMed
6 hours ago
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- Study focuses on identifying predictive markers of glofitamab resistance in relapsed/refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL).
- Patient-derived lymphoma spheroids (PDLS) from 39 R/R B-NHL samples were used to assess ex-vivo treatment response to glofitamab.
- High responders to glofitamab had CD8+ T-cells with higher cytotoxic and activation signatures.
- Low responders showed enrichment of exhausted CD8+ T-cells with markers like TIGIT, LAG3, and PD1.
- Low responders also exhibited elevated functional CD4+ T-follicular helper (Tfh) cells promoting malignant B-cell survival via IL21 and CXCL13 signaling.
- Pretreatment RNA-seq data from 48 R/R B-NHL patients confirmed high Tfh abundance correlates with poor glofitamab response.
- Anti-TIGIT co-treatment enhanced glofitamab efficacy in low responders, and Tfh depletion increased B-cell depletion.
- CD8+ T-cell exhaustion and activated Tfh cells are key factors in glofitamab resistance.
- Findings support using these markers as predictive biomarkers for patient selection and future combination therapies.