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December 8, 2025BloodOpen Access

Combinations of high risk cytogenetic events in multiple myeloma drive distinct immune remodeling patterns and worse outcomes

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Authors

CAChaitanya R. AcharyaMDMadhav V. DhodapkarSPSamir Parekh

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Overview

Combinations of high-risk cytogenetic alterations worsen progression free survival in multiple myeloma, indicating unique immune remodeling patterns.

Key Points

  • Investigate the impact of multi-hit high risk cytogenetic alterations on the immune microenvironment and patient outcomes in multiple myeloma.
  • Analyzed single-cell RNA sequencing data from 337 newly diagnosed MM patients.
  • Classified patients as multi-hit high-risk based on cytogenetic events like NSD2 t(4;14) and gain of 1q21.
  • Compared immune microenvironment and progression free survival between multi-hit and single-hit patients.
  • Multi-hit high risk patients displayed worse progression free survival (HR=2.34, p<7.2e-5) compared to standard risk patients.
  • Few patients with single-hit alterations showed non-significant trends towards worse outcomes (HR=1.51, p=0.071).
  • Distinct immune remodeling patterns were observed in multi-hit high-risk patients including reduced IFN-I stimulated T cell populations.

Cite This Study

Acharya et al. (2025) studied this question.

synapsesocial.com/papers/69362f694fa91c937236de87https://doi.org/10.1182/blood-2025-2179
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