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December 8, 2025BloodOpen Access

An acquired immune-metabolic shift to common chemotherapy confers resistance to immunotherapies in relapsed, high-risk multiple myeloma

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Authors

ESEmilia StanojkovskaHFH FischerMKMark Kramer

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Overview

Findings reveal chemotherapy alters T-cell function and metabolite levels in high-risk multiple myeloma, suggesting immunotherapy may be hindered.

Key Points

  • This research investigates the immune-metabolic dynamics in high-risk multiple myeloma patients and their response to chemotherapy.
  • Collected bone marrow aspirates from 221 multiple myeloma patients and analyzed CD138-positive plasma cells.
  • Utilized micro-array SKY92 MMProfiler for gene expression and flow cytometry for T-cell analysis.
  • Examined metabolic components using liquid chromatography-mass spectrometry for water-soluble metabolites.
  • Reduced T-cell numbers and increased CD8a+/CD4+ T-cell ratios in high-risk patients were observed.
  • Naïve T-cell depletion was confirmed in high-risk patients with significant differences in gene expression.
  • High-risk patients had elevated glutathione and depleted essential amino acids, suggesting a suppressive microenvironment.

Cite This Study

Stanojkovska et al. (2025) studied this question.

synapsesocial.com/papers/69362f444fa91c937236d5efhttps://doi.org/10.1182/blood-2025-3938
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Also Consider

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

  1. 1Dissecting the multiple myeloma survival niche to improve novel treatment strategies2025
  2. 2Shared immune features correspond to high-risk multiple myeloma across multiple human subtypes and murine models2025
  3. 3How to approach the high-risk myeloma from induction through relapse?2025 · 1 citations
  4. 4Abstract 7431: Metabolic correlates of measurable residual disease following high dose melphalan conditioning for autologous stem cell transplant in multiple myeloma2026
  5. 5Validation and refinement of the new high-risk multiple myeloma (HRMM) criteria in relapsed or refractory patients treated with BCMA CAR-T.2025