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December 8, 2025BloodOpen Access

Single-cell immune profiling reveals enhanced immune fitness of endogenous and engineered T cells in patients with high-risk smoldering myeloma compared to Relapsed/Refractory myeloma following bispecific antibodies or CAR-T cell therapies.

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Authors

FCFrancesco CorradoNBNayda BidikianMTMichael Timonian

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Overview

Single-cell sequencing shows improved immune responses to bispecific antibodies and CAR-T cells in high-risk smoldering myeloma, indicating more favorable outcomes.

Key Points

  • To evaluate immune fitness in patients with high-risk smoldering myeloma (HRSMM) compared to those with relapsed/refractory myeloma (RRMM) after immunotherapies.
  • Conducted single-cell RNA and T cell receptor sequencing on blood and bone marrow samples.
  • Compared immune responses in patients with HRSMM and RRMM after CAR-T cell and bispecific antibody treatments.
  • Analyzed T cell profiles, including stemness genes and activation markers post-treatment.
  • HRSMM patients had a higher frequency of CAR-T cells with a CD4+ phenotype expressing stemness genes.
  • At Day 28, HRSMM patients' CAR-T cells showed less exhaustion and more polyclonal nature than RRMM patients.
  • Significant upregulation of T cell activation markers was only observed in HRSMM patients.

Cite This Study

Corrado et al. (2025) studied this question.

synapsesocial.com/papers/69362f5d4fa91c937236dca6https://doi.org/10.1182/blood-2025-921
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