Product-intrinsic NF-κB-driven transcriptional programs connote durability of CAR-T response in multiple myeloma.

Elevated NF-κB activity in CD4 CAR-T cells predicts durable responses and improved survival in multiple myeloma patients treated with ide-cel.

• Why it matters: Understanding the intrinsic features that distinguish long-lasting responders from those who relapse quickly can improve patient outcomes and guide CAR-T therapy optimization.
• What they did: Single-cell RNA sequencing of 40 ide-cel products identified a transcriptional program involving NF-κB signaling, prosurvival circuits, and high CAR expression associated with durable responses, with validation showing NF-κB activity as an intrinsic marker of T-cell fitness present before manufacturing.
• The result: Targeting NF-κB pathways could enhance CAR-T efficacy, as its activity correlates with T-cell quality and response durability, providing a potential biomarker and therapeutic target to improve multiple myeloma treatment.