Organ-Specific Inflammation Mimics Relapse in CAR T-Cell Therapy Remission

Recent research conducted by Friedrich-Alexander-Universität Erlangen-Nürnberg has uncovered a new, organ-specific toxicity associated with CD19-targeted CAR T-cell therapy in autoimmune diseases. This syndrome, named local immune effector cell-associated toxicity syndrome (LICATS), was observed to affect 77% of patients undergoing treatment and consistently resolved without causing long-term damage.

Autoimmune conditions like systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myopathies involve persistent immune cell infiltration and antibody buildup, damaging various organs. Standard treatments aim to suppress immune activity but often fall short of establishing durable immunologic tolerance. While circulating B cells can be targeted with monoclonal antibodies, these do not reach immune cells entrenched within tissues, allowing continued organ deterioration despite declines in blood B-cell markers.

CAR T-cell therapy introduces genetically engineered immune cells capable of infiltrating tissues and eradicating CD19-positive B cells at affected sites. This approach has shown promising instances of drug-free remission in autoimmune patients, drawing considerable clinical interest. However, concerns about potential autoimmune-specific toxicities, beyond the well-known side effects seen in cancer trials, remain unresolved.

In a recent study published in The Lancet Rheumatology, investigators documented organ-focused reactions following CD19 CAR T-cell infusions. The study involved 39 adolescents and adults who received second-generation CD19 CAR products, including MB-CART 19.1 or KYV-101, from March 2021 to October 2024, with at least 30 days of follow-up. Medical teams monitored symptoms, lab results, imaging, and biopsies, grading events from 1 (self-resolving) to 4 (intensive care) and categorizing the timing of onset.

A total of 54 LICATS events were recorded across 30 patients, most frequently presenting as skin eruptions (35%) and kidney dysfunction (22%). Typically appearing around 10 days post-infusion and lasting approximately 11 days, all events occurred during B-cell aplasia and exclusively affected organs previously involved in each patient's autoimmune disease. Most episodes (65%) resolved spontaneously, while 30% responded to short courses of glucocorticoids. Only three patients experienced extended hospitalization due to grade 3 reactions, but none required intensive care, and all recovered fully.

The findings indicate that LICATS constitutes a self-limiting, organ-specific toxicity triggered by CD19 CAR T-cell therapy in autoimmune conditions. These events typically resolve on their own or with brief steroid treatment and do not indicate a relapse of the underlying disease.

Enhanced awareness of LICATS can help clinicians avoid unnecessary prolonged immunosuppression in post-treatment patients showing localized symptoms, thus improving management strategies and patient outcomes.