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Case Reports
. 2025 Sep 3;33(9):4135-4142.
doi: 10.1016/j.ymthe.2025.06.042. Epub 2025 Jun 28.

CD19xCD3 T cell engager blinatumomab effective in refractory generalized myasthenic syndromes

Tobias Ruck  1 , Niklas Huntemann  2 , Menekse Öztürk  3 , Stefanie Schreiber  4 , Stefanie Lichtenberg  2 , Lars Masanneck  2 , Christopher Nelke  3 , Hend Ben Moussa  2 , Thomas Ulrych  5 , Marc Seifert  5 , Dimitrios Mougiakakos  6 , Sascha Dietrich  5 , Sven G Meuth  2
Affiliations
Case Reports

CD19xCD3 T cell engager blinatumomab effective in refractory generalized myasthenic syndromes

Tobias Ruck et al. Mol Ther. .

Abstract

In this case series, we report the first off-label use of the CD19xCD3 T cell engager blinatumomab in two patients with generalized myasthenia gravis (MG). Refractory MG remains a major therapeutic challenge, with patients experiencing severe disability and potentially life-threatening crises despite intensive immunotherapy. This study evaluates the clinical efficacy and safety of short-term blinatumomab treatment in two patients with severe, refractory generalized MG. Both individuals had been experiencing persistent disease burden with myasthenic crises leading to severe disability, despite multimodal immunotherapy. Following treatment with blinatumomab, both patients showed rapid and sustained clinical improvements, reflected in significant reductions in MG-specific scores (MG Activities of Daily Living scale, Quantitative MG score, and revised MG Quality of Life-15), further patient-reported outcomes, digital activity markers, and gait analyses. Laboratory findings revealed persistent B cell depletion in patient 1, whereas patient 2 demonstrated clinical improvement and autoantibody reduction despite B cell repopulation by day 106. Both patients experienced grade 1 cytokine release syndrome during initial treatment phases, but no neurotoxicity or severe adverse events were observed. This report underscores the potential of CD19xCD3 T cell engagers as a promising therapeutic approach in severe autoimmune neuroimmunological disorders, warranting further investigation in clinical trials and mechanistic studies.

Keywords: BiTE; LEMS; Lambert-Eaton myasthenic syndrome; MG; T cell engager; blinatumomab; myasthenia gravis; neuroimmunology; neuromuscular disease; refractory MG.

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Conflict of interest statement

Declaration of interests T.R. received honoraria for lecturing, consulting, travel expenses for attending meetings, and research support from Alexion, Argenx, Biogen, BMS, Celgene, Genzyme, J&J, Merck, Novartis, Roche, Sanofi, and UCB. His research was funded by the Deutsche Gesellschaft für Muskelkranke (DGM) e.V., German Ministry for Education and Research (BMBF), German Research Foundation (DFG), Else Kroner-Fresenius Foundation, and Interdisciplinary Center for Clinical Studies (IZKF) Muenster, all outside the scope of this work. N.H. received honoraria for lecturing, consulting, travel expenses for attending meetings, and research support from Alexion, ArgenX, Janssen-Cilag, Merck, Novartis, UCB, and Viatris. His research has been funded by the DFG, outside the scope of this work. M.Ö. received honoraria for lecturing, travel expenses for attending meetings, and research support from Amicus Therapeutics, Argenx, CSL Behring, and Novartis. S.S. received research support from the DFG, Else Kroner-Fresenius Foundation, and the Federal Ministry for Economic Affairs and Energy. L.M. received honoraria for lecturing, consulting, travel expenses for attending meetings, and research support from Alexion, Argenx, B. Braun Foundation, Biogen, Merck, Neuraxpharm, Novartis, Roche, and Sanofi. His research was funded by the DFG and Deutsch Multiple Sklerose Gesellschaft (German Multiple Sclerosis Foundation), all outside the scope of this work. He is chair of the German Society for Digital Medicine. C.N. received honoraria for lecturing and consulting from Alexion and ArgenX. D.M. received honoraria for lecturing, consulting, and travel expenses for attending meetings from AbbVie, AstraZeneca, AvenCell, Beigne, BMS, Galapagos, Gilead, Janssen, Lilly, Kyverna Therapeutics, Miltenyi Novartis, Pfizer, and Roche. S.D. received honoraria for lecturing, consulting, travel expenses for attending meetings, and research support from BeiGene, BMS, Celgene, Johnson & Johnson, Kilte/ Gliead, Novartis, Pierre Fabre, and Roche. His research was supported by the BMBF (German Ministry of Education and Research) and DFG. S.G.M. received honoraria for lecturing, consulting, travel expenses for attending meetings, and research support from Academy 2, Argenx, Alexion, Almirall, Amicus Therapeutics Germany, AstraZeneca, Bayer HealthCare, Biogen, BioNTech, BMS, Celgene, Datamed, Demecan, Desitin, Diamed, Diaplan, DIU Dresden, DPmed, Gen Medicine and Healthcare products, Genzyme, Hexal AG, IGES, Impulze GmbH, Janssen Cilag, KW Medipoint, MedDay Pharmaceuticals, Medmile, Merck Serono, MICE, Mylan, Neuraxpharm, Neuropoint, Novartis, Novo Nordisk, ONO Pharma, Oxford PharmaGenesis, QuintilesIMS, Roche, Sanofi, Springer Medizin Verlag, STADA, Chugai Pharma, Teva, UCB, Viatris, Wings for Life International, and Xcenda. His research is funded by the BMBF, German Federal Institute for Risk Assessment, DFG, Else Kroner-Fresenius Foundation, Gemeinsamer Bundesausschuss, German Academic Exchange Service, Hertie Foundation, IZKF Muenster, German Foundation for Neurology, Ministry of Culture and Science of the State of North Rhine-Westphalia, the Daimler and Benz Foundation, DMSG (German Society for Multiple Sclerosis), Peek & Cloppenburg Düsseldorf Foundation, Hempel Foundation for Science, Art and Welfare, German Alzheimer Society e.V. and Alexion, Almirall, Amicus Therapeutics Germany, Argenx, Bayer Vital GmbH, BGP Products Operations (Viatris Company), Biogen, BMS, Demecan, Diamed, DGM e.v., Fresenius Medical Care, Genzyme, Gesellschaft von Freunden und Förderern der Heinrich-Heine-Universität Düsseldorf e.V., HERZ Burgdorf, Hexal, Janssen, Merck Serono, Novartis, Novo Nordisk Pharma, ONO Pharma, Roche, and Teva.

References

    1. Gilhus N.E., Tzartos S., Evoli A., Palace J., Burns T.M., Verschuuren J.J.G.M. Myasthenia gravis. Nat. Rev. Dis. Primers. 2019;5:30. doi: 10.1038/s41572-019-0079-y. - DOI - PubMed
    1. Howard J.F., Utsugisawa K., Benatar M., Murai H., Barohn R.J., Illa I., Jacob S., Vissing J., Burns T.M., Kissel J.T., et al. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017;16:976–986. doi: 10.1016/S1474-4422(17)30369-1. - DOI - PubMed
    1. Vu T., Meisel A., Mantegazza R., Annane D., Katsuno M., Aguzzi R., Enayetallah A., Beasley K.N., Rampal N., Howard J.F. Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis. NEJM Evid. 2022;1 doi: 10.1056/EVIDoa2100066. - DOI - PubMed
    1. Howard J.F., Bresch S., Genge A., Hewamadduma C., Hinton J., Hussain Y., Juntas-Morales R., Kaminski H.J., Maniaol A., Mantegazza R., et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22:395–406. doi: 10.1016/S1474-4422(23)00080-7. - DOI - PubMed
    1. Howard J.F., Bril V., Vu T., Karam C., Peric S., Margania T., Murai H., Bilinska M., Shakarishvili R., Smilowski M., et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021;20:526–536. doi: 10.1016/S1474-4422(21)00159-9. - DOI - PubMed

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