Journal Article

Anti-CD19 CAR T cells for refractory myasthenia gravis

Borie, Dominic, Wolleschak, Denise, Desel, Christiane, Motte, Jeremias, Schett, Georg, Böttcher, Martin, Haghikia, Aiden, Gold, Ralf, Hegelmaier, Tobias, Mougiakakos, Dimitrios, Schroers, Roland

2023

Overview

Building upon a study published in The Lancet Neurology showing the feasibility of transiently expressed B-cell maturation antigen (BCMA)-targeted RNA chimeric antigen receptor (CAR) T-cell therapy in patients with myasthenia gravis,1 we report a case that indicates that a different CAR T-cell approach that targets CD19 with a stably expressed CAR, delivered following a conventional lymphodepleting regimen, might be safe and effective in the treatment of severe and refractory myasthenia gravis. Previous treatment attempts, including thymectomy (in April, 2022, performed at another academic centre), acetylcholinesterase inhibitors (initiated in 2012 at our institution), and B-cell-depleting antibodies (rituximab, administered in April and October, 2021, at our institution) did not stabilise the disease course, which was class V according to the Myasthenia Gravis Foundation of America criteria (defined as intubation, with or without mechanical ventilation, except when used during routine postoperative management).3 Moreover, a proteasome inhibitor (bortezomib, administered in May and November, 2022), immunosuppressive drugs (mycophenolate mofetil, administered for 21 months preceding the CAR T-cell infusion), and immunoglobulin therapy (initiated in October, 2021) had proven futile in providing long-term relief (appendix p 4). The serological findings were paralleled by the patient's improved muscle strength and fatigue over the first 2 months after CD19 CAR T infusion, evidenced by the steady increase in the time that the patient could hold out her arm horizontally, her enhanced walking ability without any supportive devices, and the reduction of the clinical multiparameter Besinger disease activity and the Quantitative Myasthenia Gravis scores3,8 (figure).

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Acetylcholinesterase / Antibodies / Antigens / Bortezomib / Case reports / CD19 antigen / Cell therapy / Chimeric antigen receptors / Cholinesterase inhibitors / Cytokines / Humans / Immunosuppressive agents / Lymphocytes / Lymphocytes B / Lymphocytes T / Mechanical ventilation / Muscle strength / Myasthenia gravis / Myasthenia Gravis - therapy / Mycophenolate mofetil / Mycophenolic acid / Neuromuscular junctions / Patients / Proteasome inhibitors / Proteasomes / Rheumatic diseases / Rituximab / T-Lymphocytes / Thymectomy / Ventilators