CAR T-Cell Therapy for Autoimmune Disease Comes With Side Effects

 

• Chimeric antigen receptor (CAR) T-cell therapy has been an exciting area of development for autoimmune disease treatment.
• Previous reports had not mentioned any particular constellation of adverse effects as being common with the treatment.
• This report describes a usually mild syndrome, dubbed LICATS, affecting about three-quarters of CAR T-cell recipients.

Researchers said they identified a particular set of adverse effects in autoimmune disease patients treated with chimeric antigen receptor (CAR) T-cell therapy.

The syndrome involves transient reactions in the organs originally targeted by the autoimmune disease, according to Georg Schett, MD, of Friedrich-Alexander-Universität in Erlangen, Germany, and colleagues. Some three-quarters of patients undergoing the therapy have shown this syndrome -- mostly mild, resolving within a couple weeks without further incident, and probably reflecting the treatment's ultimately beneficial effects.

Schett's group, in a report appearing in The Lancet Rheumatologyopens in a new tab or window, called the syndrome "immune effector cell-associated toxicity syndrome" or LICATS.

"Knowledge about LICATS is crucial to prevent misinterpretation and unnecessary immunosuppression," the researchers wrote. "We therefore suggest LICATS as a new adverse event that should be assessed in future CAR T-cell trials in autoimmune disease."

Schett has been the prime mover behind use of CAR T-cell therapy -- first developed as a blood cancer treatment -- in autoimmune disease. An early report in 2022opens in a new tab or window indicated that it looked almost like a cure in five patients with systemic lupus erythematosus (SLE). Several others have emerged since, with more patients and a wider range of autoimmune conditionsopens in a new tab or window, including systemic sclerosis (SSc) and inflammatory immune myositis (IIM). Nearly all patients have shown dramatic improvement, many no longer requiring conventional therapy, with remissions lasting as long as they've been followed.

Until now, these reports didn't include any suggestions of adverse effects occurring commonly with the therapy, in which patients' T cells are extracted and modified ex vivo to express receptor proteins that bind to a specific antigen on other cells that need to be eliminated. These transformed T cells are then reinjected into the patient, where they hunt down and kill the target cells (B cells thus far).

The new report covers 39 patients with SLE (n=20), SSc (n=13), and IIM (n=6) who have received CAR T-cell therapy from Schett's group. Of these, 30 developed symptoms that reflected "cleansing of immune cells from the affected organs," and were distinct from cytokine release syndrome, which typically includes systemic symptoms such as fever that did not appear in these patients.

Particular symptoms varied according to which organs were involved in the individual patients' disease. Thus, patients whose autoimmune condition had hit their muscles had muscle-related issues such as elevations in creatinine kinase. Patients with renal impairments showed transient worsening in kidney function, and so forth.

Schett and colleagues developed a grading system for LICATS in which symptoms that resolved without treatment was grade 1; symptoms calling for corticosteroid treatment was grade 2; LICATS requiring new or extended hospitalization was grade 3; and need for intensive care was grade 4.

No grade 4 events were seen and just three involved hospitalization and thus merited grade 3. In all, 65% of LICATS episodes were grade 1, and 30% reached grade 2. Median time to onset from CAR-T cell infusion was 10 days across all patients (interquartile range 9-21). Median duration was 11 days (IQR 5-14). Among patients given prednisolone for LICATS, the median cumulative dose was 172 mg (IQR 112-215).

While LICATS seemed different from cytokine release syndrome, the latter did occur in as many patients. This, too, never became serious.

LICATS appeared to develop during the period when the therapy had completely eliminated patients' B cells, indicating that the symptoms did not stem from disease flares. Biopsies from a few patients showed myeloid cells, an indication that "cleansing processes" were underway in the affected organs.

Why hasn't anything like LICATS been reported with CAR T-cell therapy in cancer patients? "It is possible that LICATS is an underreported phenomenon in hemato-oncology," Schett and colleagues offered, "but it could also be the case that LICATS indeed is less common following CD19-targeting CAR T-cell therapy of B-cell malignancies, as the organ distribution of malignant B cells follows other principles than the tissue infiltrates in B-cell driven autoimmune diseases."

In an accompanying commentaryopens in a new tab or window, two scholars from the University of California Los Angeles concurred that, on the basis of these findings, LICATS doesn't seem like a huge problem with CAR T-cell therapy in autoimmune disease.

Still, according to Samuel Good, MD, and Elizabeth Volkmann, MD, MS, "a number of questions and unresolved issues remain." These include a need for larger studies, in part to assess the potential for LICATS in critical organs such as the lungs to cause serious complications.

Good and Volkmann also called for future CAR T-cell studies in autoimmune disease to be run as controlled trials with comparator groups.

Disclosures

The study was supported by the Deutsche Forschungsgemeinschaft, German Cancer Aid, Bundesministerium für Bildung und Forschung, European Union, Staedtler Foundation, Lupus Research Alliance, and the Bendel and Bleyl families.

Study authors reported relationships with a large number of pharmaceutical companies and other commercial entities.

Good declared he had no relevant financial interests. Volkmann reported relationships with Kadmon, GSK, Atyr Pharma, Boehringer Ingelheim, Horizon, Prometheus, and AbbVie.

Primary Source

The Lancet Rheumatology

Source Reference: opens in a new tab or windowHagen M, et al "Local immune effector cell-associated toxicity syndrome in CAR T-cell treated patients with autoimmune disease: an observational study" Lancet Rheumatol 2025; DOI: 10.1016/S2665-9913(25)00091-8.

Secondary Source

The Lancet Rheumatology

Source Reference: opens in a new tab or windowGood SD, et al "A new toxicity syndrome in patients with autoimmune disease treated with CAR T-cell therapy" Lancet Rheumatol 2025; DOI: 10.1016/S2665-9913(25)00100-6.

https://www.medpagetoday.com/rheumatology/generalrheumatology/115412