Anti-BCMA/CD19 CAR T cell therapy in patients with refractory generalized myasthenia gravis: a single-arm, phase 1...

Treating refractory generalized myasthenia gravis is still a big challenge, so new treatments are needed. Several studies have shown the potential of chimeric antigen receptor (CAR) T cell therapy in the treatment of autoimmune diseases. However, no clinical trial of bispecific CAR T cells targeting refractory myasthenia gravis has been done. We developed autologous anti-B-cell maturation antigen (BCMA) and CD19 bispecific CAR T cells to evaluate the safety and efficacy in refractory myasthenia gravis.

This single-arm, phase 1 trial (ChiCTR2200061267) was conducted at the Affiliated Hospital of Xuzhou Medical University in refractory generalized myasthenia gravis patients (Myasthenia Gravis Activities of Daily Living [MG-ADL] ≥6-point, and Quantitative Myasthenia Gravis scale [QMG] ≥8-point). Anti-BCMA/CD19 bispecific CAR T cells were administered at 1.0 × 10⁶, 3.0 × 10⁶, and 5.0 × 10⁶ CAR T cells per kg. Primary endpoints assessed safety (dose-limiting toxicities, maximum tolerated dose, and adverse events); secondary endpoints assessed disease severity and other related indexes.

Between May 3, 2023, and June 19, 2024, 18 patients were enrolled and received apheresis and a single CAR T cell infusion. Mean age was 41 years (SD 12) and 12 (67%) participants were female. The anti-BCMA/CD19 bispecific CAR T cells were generally safe, with no dose-limiting toxicities, no immune effector cell-associated neurotoxicity syndrome, and only grade 1 cytokine release syndrome (39% of patients). The most common grade 3 or worse adverse events within 28 days were hematological toxicities, including three leukopenia, three neutropenia, one anaemia, and one thrombocytopenia. All were transient and manageable. 17 participants completed follow-up. Clinical improvements by day 180 were -8.6 (95% CI -10.2 to -7.0) for MG-ADL score and -15.4 (-17.6 to -13.2) for QMG score. 14 participants (82%) achieved minimal manifestations, 15 (88%) stopped glucocorticoids, all stopped non-steroidal immunosuppressants, and eight (47%) had anti-acetylcholine receptor antibody negative seroconversion.

Anti-BCMA/CD19 CAR T cells showed good safety and efficacy in refractory generalized myasthenia gravis. A large proportion of participants had a minimal manifestation status and discontinued glucocorticoids and non-steroidal immunosuppressants, and a certain proportion of anti-acetylcholine receptor antibodies turned negative.

National Natural Science Foundation of China, Basic Research Program of Jiangsu, Young academic leaders of Jiangsu Qinglan Project, and Construction Project of High Level Hospital of Jiangsu Province.