Chimeric antigen receptor T-cell therapy in autoimmune rheumatic diseases: defining the reset-opportunity window.

The current challenge in autoimmune chimeric antigen receptor (CAR) T-cell therapy is no longer whether B cells can be depleted, but whether treatment is delivered before immune-mediated organ injury has become irreversible. This targeted narrative review appraises CD19-directed, dual CD19/B-cell maturation antigen, B-cell maturation antigen-directed and allogeneic approaches in systemic lupus erythematosus, systemic sclerosis and idiopathic inflammatory myopathies. It proposes a reset-opportunity window: a pre-treatment state in which active immune injury, targetable B-lineage or plasma-cell biology and residual organ reserve coexist. Systemic lupus erythematosus is the clearest current test case because serology, complement, renal activity and remission can be followed serially. Systemic sclerosis and myositis require more cautious interpretation because fibrosis, vasculopathy and fatty muscle replacement may limit recovery despite immune control.To make partial and negative responses interpretable, the review defines five failure domains: cellular-product failure, target/plasma-cell escape, reconstitution failure, organ-reserve failure and comparator failure. The first four are patient-level mechanistic phenotypes; comparator failure is a trial-level interpretive domain. These domains are non-exclusive and may coexist within the same clinical course or dataset.Trials should make response and non-response mechanistically interpretable: they should report screened-but-not-infused patients, CAR T-cell expansion, B-cell and plasma-cell reconstitution, baseline damage, organ-specific recovery and relapse after immunereconstitution. Without these data, a clinical response cannot be distinguished from favourable selection, temporary depletion or damage-limited stabilisation.