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TOPLINE:

A substantial proportion of patients with autoimmune diseases experienced a new side effect called local immune effector cell–associated toxicity syndromes (LICATS) after receiving chimeric antigen receptor (CAR) T-cell therapy; these effects were usually mild, self-limited, and occurred in organs previously affected by the autoimmune condition.

METHODOLOGY:

• Researchers conducted this observational study to investigate the safety of CD19-targeting CAR T-cell therapy in patients with autoimmune diseases.
• They included 39 patients (median age, 36 years; 64% women), of whom 20 had systemic lupus erythematosus, 13 had systemic sclerosis, and 6 had idiopathic inflammatory myopathy.
• All patients underwent lymphodepletion with cyclophosphamide and fludarabine followed by CAR T-cell infusion and were followed for at least 1 month.
• Observed reactions after CD19-targeting CAR T-cell infusion were classified on the basis of localization, time of onset, duration, and severity.
• Severity was graded from 1 (spontaneous resolution) to 4 (intensive care treatment), and the time of onset was classified as early (up to 2 weeks), intermediate (between 2 weeks and 1 month), and late (beyond 1 month) after CAR T-cell administration.

TAKEAWAY:

• A total of 54 events of LICATS were observed, affecting 30 (77%) patients, of which 15 patients had more than one manifestation of LICATS.
• LICATS occurred at a median of 10 days post–CAR T-cell infusion and lasted for a median of 11 days. Regarding the onset of events, 50% of them occurred within the first 2 weeks, 30% between 2 weeks and 1 month, and 20% after 1 month of CAR T-cell administration.
• The severity of events of LICATS was mostly mild (grade 1, 65%), with only three patients requiring prolonged or new hospitalization. All events of LICATS occurred during B-cell aplasia and in organs previously affected by the autoimmune disease.
• The most common manifestations of LICATS were transient skin rashes (35%), a worsening of kidney function or proteinuria (22%), and musculoskeletal symptoms (19%).

IN PRACTICE:

“LICATS typically occurred during the period of time when CAR T cells peaked, suggesting an immunological basis for this clinical phenomenon. This distinction has important implications, as clinicians might want to escalate immunosuppression for patients in whom a flare is suspected. Increased education and awareness of LICATS could avert unnecessary use of added immunosuppression following CAR T-cell infusions,” experts wrote in an accompanying editorial.

SOURCE:

This study was led by Melanie Hagen, MD, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. It was published online on April 30, 2025, in The Lancet Rheumatology.

LIMITATIONS:

In this study, only a limited number of biopsies were taken from the skin, gastrointestinal tract, and kidneys, potentially restricting a comprehensive understanding of the tissue-specific effects of LICATS. The absence of a comparator group is another major drawback of this study.

DISCLOSURES:

This study received funding from Deutsche Forschungsgemeinschaft, German Cancer Aid, Bundesministerium für Bildung und Forschung, and other sources. Some authors reported receiving grants, honoraria, consultancy fees, support for attending meetings, and other ties from various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.