1537: Local Immune effector Cell-Associated Toxicity Syndrome (LICATS) in CAR T-cell treated patients with Autoimmune Disease

Background/Purpose: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment strategies for severe B-cell driven autoimmune diseases (AID) like Systemic Lupus erythematosus (SLE), Systemic Sclerosis (SSc) or Idiopathic Inflammatory Myositis (IIM). Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and hematotoxicity are the most common and best described side effects, but little is known about AID-specific adverse events (1,2).
Purpose of our study was to describe a new form of toxicity – Local Immune effector cell-Associated Toxicity Syndrome (LICATS), related to the treatment of patients with autoimmune disease (AID) with CD19-targeting chimeric antigen receptor (CAR) T-cells.

Methods: AID patients receiving CD19-CAR T-cell therapy in Erlangen and Duesseldorf with a follow-up of at least 30 days were assessed for organ-specific LICATS occurring after CAR T-cell infusion. Observed reactions were documented according to localization, time, duration and graded for severity (grade 1: spontaneous resolution; grade 2: glucocorticoid use; grade 3: glucocorticoid use plus prolonged hospital stay; grade 4: intensive care treatment). No systemic events, such as fever, chills, nausea, fatigue, diffuse pain/hypersensitivity or hemodynamic changes were classified as LICATS to separate it from CRS. Furthermore, per definition, LICATS were time-limited events that spontaneously regressed or stopped after a short course of glucocorticoid treatment in order to distinguish it from recurrence of AID.

Results: Between March 2021 and October 2024, 39 patients with AID were treated with CD19-CAR T-cells (20 systemic lupus erythematosus, SLE; 13 systemic sclerosis, SSc; 6 idiopathic inflammatory myositis, IIM). 25 patients (64.1%) were females. Median age was 36 years [22;43.5]. 54 local reactions, which we termed “Local Immune effector Cell-Associated Toxicity Syndrome” (LICATS) were recorded, affecting overall 30 patients (76.9%) with median (IQR) time of onset of 14 [5;21] days and a median duration of 11 [5;14] days. LICATS exclusively occurred during the B-cell aplasia phase and only involved organs previously affected by the respective AID. Most frequent affected organs were the skin (N=19, 35.2%) and the kidneys (N=12, 22.2%). Most LICATS were mild (grade 1: 35, grade 2: 16). Only three LICATS were grade 3. All LICATS resolved without sequelae.

Conclusion: LICATS is a new form of toxicity in CD19-CAR T-cell treated patients with AID, most likely based on the cleansing of immune cells from the affected organs. It is self-limited, organ-specific and usually mild in its intensity.


References:

< !1. Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024; 390:687-700.

< !2. Isaacs JD. CAR T Cells - A New Horizon for Autoimmunity?. N Engl J Med. 2024; 390:758-759.