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Immune Atlas Sharpens Myeloma Risk Prediction as Dual-Target CAR T Counters BCMA Loss

Linking baseline bone marrow immune states to outcomes points to tests that could steer treatment.

Overview

  • A Nature Cancer study profiled about 1.4 million single cells from 337 newly diagnosed patients using MMRF CoMMpass data, with validation in 74 additional patients and over 240,000 cells.
  • Baseline immune states, including a dysfunctional or senescent T-cell phenotype and inflammatory tumor–immune signaling, were tied to early relapse and more aggressive disease biology.
  • Integrating immune signatures with tumor cytogenetics improved risk stratification and survival prediction beyond genetics alone, according to the validated analysis.
  • Separately, a preclinical Molecular Therapy report showed bispecific BAFF-R/BCMA CAR T cells controlled heterogeneous myeloma and remained effective when BCMA was absent in lab and patient-derived models.
  • Authors report that 5% to 30% of patients might particularly benefit from the dual-target approach, with screening tests and first-in-human trials needed to establish clinical utility.