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Comparison of the safety profiles of CD19-targeting CAR T-cell therapy in patients with SLE and B-cell lymphoma

Researchers at University Hospital Erlangen and collaborators have observed that CD19 CAR T-cell therapy has a more favorable safety profile in systemic lupus erythematosus (SLE) than in B-cell non-Hodgkin lymphoma, despite similar CAR T-cell expansion following infusion. In this comparative brief report, patients with SLE experienced lower incidence and severity of cytokine-release syndrome, neurotoxicity consistent with Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and immune effector cell–associated hematotoxicity. Although neutrophil nadirs dipped lower in SLE, platelet counts remained near normal, with the duration of cytopenias being shorter than in B-NHL. CAR T-cell persistence was consistently shorter in SLE, while reconstitution of the adaptive immune system was faster, with earlier recovery of conventional T and B cells.

The investigators note that lymphodepletion intensity and CAR T pharmacokinetics were comparable across cohorts, which points to host biology and inflammatory tone as key drivers of toxicity differences. Reduced hematotoxicity in SLE was correlated with lower acute-phase inflammation at baseline, greater hematologic reserve prior to therapy, and distinct serum cytokine patterns. In both diseases, B-cell reconstitution tracked with functional CD4 T-cell recovery, suggesting a shared program of immune system regeneration following transient CAR T persistence and B-cell aplasia. These observations help reconcile why patients with high autoimmune inflammation can still experience milder acute toxicities than oncology patients who often present with cumulative marrow injury and systemic inflammatory signals from tumor and prior treatments.

Clinically, the findings support CD19 CAR T as a promising option for refractory SLE, with both manageable safety and quicker immune recovery, which may influence inpatient monitoring needs, antimicrobial prophylaxis duration, and the timing of revaccination. For B-NHL, the data reinforce expectations of longer hematotoxicity and higher rates of CRS and ICANS, underscoring the value of pre-infusion risk assessment and supportive care. The study is observational and brief in scope, with product heterogeneity and cohort size limiting firm causality. With this said, the consistent pattern across kinetics, toxicity, and immune reconstitution argues that disease context shapes CAR T tolerability, with SLE showcasing a distinctly safer profile than B-NHL.

Reference:

Müller F, Schwingen NR, Hagen M, et al. Comparison of the safety profiles of CD19-targeting CAR T-cell therapy in patients with SLE and B-cell lymphoma. Blood. 2025;146(9):1088-1095.

http://doi.org/10.1182/blood.2025028375