German rheumatologists conducted an observational study and identified a previously unknown side effect of therapy for autoimmune diseases with lymphocytes with chimeric antigen receptors. It is probably associated with the abrupt elimination of immune cells from the affected tissues. In most cases, this complication is not severe and goes away on its own over time. A report on the work was published in The Lancet Rheumatology.
The technology of chimeric antigen receptors T-lymphocytes (CAR-T-lymphocytes; detailed in the article “Chimera vs. Cancer”) was developed and is used primarily for the treatment of malignant neoplasms. The greatest success has been achieved in the treatment of B-cell oncohematological neoplasms with autologous anti-CD19-CAR-T-lymphocytes. At the same time, in pilot clinical trials, similar cells were successfully used to treat various severe autoimmune diseases (the editors of the journal Science, like Nature, called these experiments one of the main scientific achievements of 2024). The most common side effects specific to this treatment method include ICANS syndrome and other manifestations of neurotoxicity, cytokine release syndrome, and hemophagocytic lymphohistiocytosis.
Georg Schett from the Friedrich-Alexander University Erlangen-Nuremberg and colleagues analyzed organ-specific responses to CD19 CAR T cell therapy for autoimmune diseases in their clinical trials. The analysis included 39 patients (median age 36 years, 64 percent women) treated at two clinical centers from March 2021 to October 2024. Of these, 20 had systemic lupus erythematosus, 13 had systemic sclerosis, and six had idiopathic inflammatory myopathy.
After treatment, 54 local toxic reactions were registered in 30 patients (77 percent). The median time of their onset was 10 days after CAR-T cell infusion, and the median duration was 11 days. All these events occurred only in the B-lymphocyte aplasia phase and affected only the organs affected by the autoimmune disease - most often, these were the skin (35 percent of events) and kidneys (22 percent). Most of these manifestations were relatively mild, only three cases were severe (prolonged hospitalization or required re-hospitalization). All of them passed without consequences.
The researchers named the new side effect local immune effector cell-associated toxicity syndrome (LICATS). They believe that temporary dysfunction of the affected organs occurs as a result of local inflammation due to massive loss of tissue-infiltrating B lymphocytes. LICATS should be differentiated from cytokine release syndrome during clinical trials, since it is local and self-limited and does not require resumption of immunosuppressive therapy, the authors of the study believe.
Previously conducted analysis of long-term outcomes of experimental CAR-T lymphocyte therapy confirmed an extremely low risk of developing new tumors after it. Also, clinical trials of the second phase showed that this method of treatment is quite effective and safe when carried out in an outpatient setting. At the same time, the main non-oncological cause of death after CAR-T therapy was infections.