Comparison of the safety profiles of CD19-targeting CAR T-cell therapy in patients with SLE and B-cell lymphoma
Fabian Müller, Nora Rebecca Schwingen, Melanie Hagen, Julia Katharina Scholz, Michael Aigner, Andreas Wirsching, Jule Taubmann, Sascha Kretschmann, Soraya Kharboutli, Tobias Krickau, Nora Naumann‐Bartsch, Giulia Benintende, Silvia Spoerl, Tobias Rothe, Heiko Bruns, Ricardo Grieshaber‐Bouyer, Markus Metzler, David B. Blumenthal, Frederik Graw, G. Schett, Andréas Mackensen, Simon Völkl
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.