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

Abstract

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 seemed to differ between patients with SLE and B-NHL. We therefore compared the CAR T-cell kinetics and treatment-related side effects to better define the toxicity profiles. In contrast with the similar CAR T-cell expansion, patients with SLE revealed a lower incidence and severity of cytokine-release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hematotoxicity. Although the neutrophil nadir was lower in patients with SLE after therapy, the platelet counts remained close to normal and hematotoxicity was shorter in SLE than B-NHL. The reduced hematotoxicity correlated with lower acute-phase inflammation, better hematologic reserve before CAR T-cell therapy, and distinct serum cytokine profiles. Interestingly, CAR T-cell persistence was consistently shorter, and the 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 biologic process of hematopoietic and immune system regeneration. In summary, similar lymphodepletion and CAR T-cell pharmacokinetics led to distinct toxicity, demonstrating that CAR T-cell therapy had a favorable side-effect profile in SLE, including faster recovery of the adaptive immune system.