A new hope with CAR T-cell therapy for refractory idiopathic inflammatory myopathies: a systematic review.

backgroundTreatment options for refractory idiopathic inflammatory myopathies (IIMs) remain limited, and sustained remission is frequently not achieved with conventional immunosuppression or biologic agents. Chimeric antigen receptor (CAR) T-cell therapy has been approved for multiple refractory hematologic malignancies and is increasingly being explored as an immune reset strategy for autoimmune diseases. MAIN BODY: This Review synthesizes all available clinical evidence on CAR T-cell therapy in adult and pediatric IIM, with the aim of raising awareness within the rheumatology community regarding its clinical application and providing an evidence-based framework to guide future therapeutic decision-making. Across 10 reports comprising 12 refractory IIM patients, CAR T-cell therapy was associated with rapid improvements in muscle enzymes and strength, meaningful treatment de-escalation with frequent drug-free remission. Safety was generally manageable, with predominantly grade 1-2 cytokine release syndrome, rare immune effector cell-associated neurotoxicity syndrome, and treatable infections. Pharmacokinetic and immunodynamic patterns were consistent, with early in-vivo expansion, rapid B-cell depletion, and reconstitution dominated by naïve and transitional phenotypes.

conclusionsEarly clinical experience supports CAR T-cell therapy as a promising experimental approach for refractory IIM, but current evidence is limited by small sample sizes, heterogeneous endpoints, and short follow-up. Prospective studies with standardized outcomes, organ-specific assessments, and long-term safety monitoring are required.