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December 8, 2025BloodOpen Access

Evidence for pre-existing myeloma cells with a gene expression pattern associated with resistance to BCMA CAR T cells.

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Authors

LHLondon HarperHLHolly LeePNPaola Neri

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Overview

RNAseq reveals pre-existing myeloma cell resistance patterns in patients, suggesting implications for CAR T therapy.

Key Points

  • To investigate mechanisms of resistance to BCMA CAR T cells in multiple myeloma and identify pre-existing resistant cells.
  • Applied spatiotemporal genomic analysis to isolate resistant myeloma cells engaged by BCMA CAR T cells.
  • Performed RNA sequencing on isolated cells to assess gene expression patterns.
  • Compared differentially expressed genes to untreated controls to identify resistance signatures.
  • Examined survival and engagement times of various myeloma cell lines when exposed to CAR T therapies.
  • Approximately 24.7% of myeloma cells remained viable after exposure to BCMA CAR T cells for 16 hours.
  • Identified 1101 commonly upregulated genes in KMS12PE and KMS26 cells, linked to inflammation and signaling pathways.
  • Resistance correlated with increased Granzyme B inhibition and altered gene expression related to viability and cell death.
  • Detectable pre-existing resistant cells in patients pre-CAR T infusion with a gene signature similar to post-infusion responses.

Cite This Study

Harper et al. (2025) studied this question.

synapsesocial.com/papers/69362f3a4fa91c937236d437https://doi.org/10.1182/blood-2025-1031
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Also Consider

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

  1. 1The dynamic landscape of immune environment for MM patients receiving T cell redirectiing therapies2025
  2. 2Abstract 6467: Myeloma cells with therapy-induced senescence-like phenotype are associated with resistance to CAR-T therapy2026
  3. 3Impact of prior BCMA-targeted therapy on CAR-T expansion and host T-cell phenotypes in patients with Relapsed/Refractory multiple myeloma receiving BCMA CAR-T therapy2025
  4. 4Abstract 3617: Expansion and persistence of anti-BCMA CAR T cells correlates with durability of responses in multiple myeloma patients2024
  5. 5Identification of persister cells and evolution of tumor clones during immunotherapy and at minimal residual disease timepoints decoded by single-cell whole-genome sequencing in multiple myeloma2025