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

Treatment 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.

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.

Early 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.