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

Abstract

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL) and recently showed effects in autoimmune diseases such as systemic lupus erythematosus (SLE). Despite high levels of inflammation, toxicity appeared to differ in SLE and B-NHL. We therefore compared CAR T-cell kinetics and treatment-related side-effects to better define the distinct toxicity profiles. Contrary to similar CAR T-cell expansion, SLE patients revealed lower incidence and severity of cytokine-release syndrome, immune-effector cell-associated neurotoxicity syndrome, and immune-effector cell-associated hematotoxicity. While neutrophil nadir was lower in SLE patients after therapy, platelets remained close to normal and hematotoxicity was shorter in SLE than in B-NHL. Reduced hematotoxicity correlated with lower acute phase inflammation, better hematological reserve prior to CAR T-cell therapy, and distinct serum cytokine profiles. Interestingly, CAR T-cell persistence was consistently shorter and reconstitution of conventional T- and B-cells was faster in SLE. In both cohorts, B-cell reconstitution correlated with functional CD4+ T-cell recovery, indicating a general biological process of hematopoietic and immune system regeneration. In summary, similar lymphodepletion and CAR T-cell pharmacokinetics resulted in distinct toxicity, demonstrating a favorable side effect profile of CAR T-cell therapy in SLE including faster recovery of the adaptive immune system.