Anti-CD19 CAR-T cells are effective in severe idiopathic Lambert-Eaton myasthenic syndrome

Wickel J, Schnetzke U, Klink A, Rinke J, Borie D, Dudziak D, Hochhaus A, Heger L, Geis C (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cell Reports Medicine Elsevier

Article Number: 101794

DOI: 10.1016/j.xcrm.2024.101794

Abstract

Lambert-Eaton myasthenic syndrome (LEMS) is an autoantibody-mediated disease of the neuromuscular junction characterized by muscular weakness. Autoantibodies to presynaptic P/Q-type voltage-gated calcium channels (VGCCs) induce defective neuromuscular function. In severe cases, current immunosuppressive and immunomodulatory treatment strategies are often insufficient. First reports show beneficial effects of anti-CD19 chimeric antigen receptor (CAR)-T cell therapy in patients with autoantibody-mediated myasthenia gravis. We report a patient with isolated idiopathic LEMS treated with autologous anti-CD19-CAR-T cells. In this patient, CAR-T infusion leads to expansion of predominantly CD4+ CAR-T cells with a terminally differentiated effector memory cells re-expressing CD45RA (TEMRA)-like phenotype indicating cytotoxic capabilities and subsequent B cell depletion. VGCC antibody titers decrease, resulting in a clinical improvement of LEMS symptoms, e.g., 8-fold increase in walking distance. The patient does not show relevant side effects except for cytokine release syndrome grade 2 and intermittent neutropenia suggesting that anti-CD19 CAR-T cell therapy may be a treatment option in patients with LEMS.

Authors with CRIS profile

Lukas Heger Department of Dermatology

Involved external institutions

Universitätsklinikum Jena DE Germany (DE) Kyverna Therapeutics, Inc. US United States (USA) (US) Mitteldeutsches Krebszentrum / Cancer Center Central Germany (CCCG) DE Germany (DE)

How to cite

APA:

Wickel, J., Schnetzke, U., Klink, A., Rinke, J., Borie, D., Dudziak, D.,... Geis, C. (2024). Anti-CD19 CAR-T cells are effective in severe idiopathic Lambert-Eaton myasthenic syndrome. Cell Reports Medicine. https://doi.org/10.1016/j.xcrm.2024.101794

MLA:

Wickel, Jonathan, et al. "Anti-CD19 CAR-T cells are effective in severe idiopathic Lambert-Eaton myasthenic syndrome." Cell Reports Medicine (2024).

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