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December 8, 2025BloodOpen Access

Concurrent TP53 loss-of-function and epigenetic modifier mutations as a potential predictor of chemoimmunotherapy failure in DLBCL & hgbl

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Authors

ARArjun RavishankarIIIris IsufiSHScott Huntington

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Overview

Retrospective analysis reveals TP53 mutations and epigenetic changes predict failure of chemoimmunotherapy in DLBCL and HGBL, indicating need for CAR-T strategies.

Key Points

  • This research aims to identify high-risk molecular signatures in DLBCL and HGBL to predict treatment outcomes to chemoimmunotherapy.
  • Retrospective analysis of 10 patients with DLBCL/HGBL treated with first-line chemoimmunotherapy
  • Comprehensive genomic profiling performed on pre-treatment tumor samples
  • Patients classified into durable complete response and relapsed/refractory groups based on therapy response
  • Statistical analysis of clinicopathologic variables using Mann-Whitney U test
  • Patients with relapsed/refractory disease exhibited a distinct molecular signature of TP53 loss-of-function mutations and epigenetic modifications
  • Approximately 40% of relapsed patients required CAR-T therapy, indicating treatment resistance
  • The dual mutation signature was absent in all durable complete response patients and most relapsed patients
  • Comprehensive genomic profiling showed that TP53 mutations may have more predictive power when evaluated alongside epigenetic dysregulation.

Cite This Study

Ravishankar et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d579https://doi.org/10.1182/blood-2025-7071
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