Time of onset, severity, and localization of LICATS. Credit: The Lancet Rheumatology (2025). DOI: 10.1016/S2665-9913(25)00091-8

Researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg have identified a previously undocumented, organ-specific toxicity linked to CD19-targeted CAR T-cell therapy in autoimmune disease. The syndrome, termed local immune effector cell-associated toxicity syndrome (LICATS), affected 77% of patients and resolved without lasting complications.

B-cell-driven autoimmune diseases such as systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myopathy damage organs through prolonged immune cell infiltration and antibody accumulation. Conventional therapies suppress immune activation but often fail to restore lasting immunologic tolerance.

Circulating B cells can be targeted by monoclonal antibodies, yet this approach does not reach immune cells embedded deep within tissues. Organs such as the kidney, lung, and muscle continue to deteriorate under local inflammation, even when blood-based B-cell markers decline.

CAR T-cell therapy introduces genetically modified immune cells capable of penetrating tissue and eliminating CD19-positive B cells in affected sites. Reports of drug-free remission in patients treated with this approach have intensified clinical interest.Toxicities observed in cancer trials dominate the risk profile, leaving clinicians uncertain about potential autoimmune-specific complications.

In the study, "Local immune effector cell-associated toxicity syndrome in CAR T-cell treated patients with autoimmune disease, " published in The Lancet Rheumatology, investigators conducted an observational analysis to document organ-focused reactions following CD19 CAR T-cell infusion.

A total of 39 adults and adolescents received the second-generation CD19 CAR products, MB-CART 19.1 or KYV-101, at Erlangen and Düsseldorf centers between March 2021 and October 2024, then entered at least 30-day follow-up.

Clinicians tracked local symptoms, laboratory shifts, imaging, and biopsy results, grading events from 1 (self-resolving) to 4 (intensive care) and classifying onset as early, intermediate, or late. Investigators excluded systemic cytokine release syndrome (CRS) and required spontaneous regression or brief glucocorticoid use to separate LICATS from disease flare.

In all, 54 LICATS events emerged across 30 patients, most often skin eruptions (35%) and kidney dysfunction (22%). Median onset registered at 10 days after infusion, lasting a median of 11 days. All events occurred during B-cell aplasia and only in organs previously involved in each patient's autoimmune disease.

Some 65% of episodes resolved without therapy, 30% responded to short glucocorticoid tapers, and only three events prompted rehospitalization. Three events, all categorized as grade 3, led to extended hospitalization. No patients required intensive care, and all LICATS events resolved without long-term impairment.

Researchers conclude that LICATS represents a self-limiting form of organ-specific toxicity arising after CD19-targeted CAR T-cell therapy in autoimmune disease. Events resolved spontaneously or with brief glucocorticoid treatment and did not signal recurrence of underlying disease.

Awareness of LICATS may help clinicians avoid unnecessary long-term immunosuppression in patients who develop post-treatment symptoms localized to previously affected organs.

More information: Melanie Hagen et al, Local immune effector cell-associated toxicity syndrome in CAR T-cell treated patients with autoimmune disease: an observational study, The Lancet Rheumatology (2025). DOI: 10.1016/S2665-9913(25)00091-8 Samuel D Good et al, A new toxicity syndrome in patients with autoimmune disease treated with CAR T-cell therapy, The Lancet Rheumatology (2025). DOI: 10.1016/S2665-9913(25)00100-6  Journal information: The Lancet Rheumatology

Samuel D Good et al, A new toxicity syndrome in patients with autoimmune disease treated with CAR T-cell therapy, The Lancet Rheumatology (2025). DOI: 10.1016/S2665-9913(25)00100-6

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