Abstract
Objective: Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular junction disorder involving the acetylcholine receptors on the motor endplate. The safety and response to high-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT) were assessed in a patient with severe refractory MG. Methods: As part of a pilot study of HDIT/HCT for patients with treatment-resistant autoimmune neurological disorders, a patient with severe refractory MG underwent treatment. After mobilization of hematopoietic stem cells with rituximab, prednisone, and G-CSF, the patient had HDIT consisting of carmustine, etoposide, cytarabine, melphalan, and rabbit antithymocyte globulin, followed by autologous HCT. The effect of treatment on the autoantibody to the acetylcholine receptor (AChR) was assessed. Results: The patient had been diagnosed with AChR antibody-positive MG 14 years before HDIT/HCT and had failed thymectomy, therapeutic plasma exchange, and multiple immunomodulatory agents. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was IVb before HDIT/HCT. She tolerated HDIT/HCT well and started to improve clinically within days of treatment. At both 1 and 2 years after HDIT/HCT, patients remained symptom-free. After HDIT/HCT, AChR-binding autoantibodies persisted, and the relative frequency of immune cell subtypes shifted. Interpretation: HDIT/HCT induced a complete response of disease activity in a patient with severe refractory MG. This response may suggest that a cell-mediated etiology may be a significant contributing factor in refractory MG cases. A phase 2 clinical trial is warranted to establish if HDIT/HCT can be an effective therapy for severe refractory MG and to gain a further understanding of disease pathogenesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2105-2113 |
| Number of pages | 9 |
| Journal | Annals of clinical and translational neurology |
| Volume | 10 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2023 |
Funding
Dr. Nowak reports research support from the National Institutes of Health, Genentech, Inc., Alexion Pharmaceuticals, Inc., argenx, Annexon Biosciences, Inc., Ra Pharmaceuticals, Inc. (now UCB S.A.), the Myasthenia Gravis Foundation of America, Inc., Momenta Pharmaceuticals, Inc., Immunovant, Inc., Grifols, S.A., and Viela Bio, Inc. (Horizon Therapeutics plc). Dr. Nowak has also served as a consultant and advisor for Alexion Pharmaceuticals, Inc., argenx, Cabaletta Bio, Inc., COUR, CSL Behring, Grifols, S.A., Ra Pharmaceuticals, Inc. (now UCB S.A.), Immunovant, Inc., Momenta Pharmaceuticals, Inc., and Viela Bio, Inc. (Horizon Therapeutics plc). Dr. Kevin C. O'Connor is supported by the National Institute of Allergy and Infectious Diseases of the NIH under award numbers R01‐AI114780 and R21‐AI164590; through a pilot award (MGNet Pilot (21‐M99) provided through the Rare Diseases Clinical Research Consortia of the NIH and MGNet (award number U54‐NS115054), and by a High Impact Clinical Research and Scientific Pilot Project award from the Myasthenia Gravis Foundation of American (MGFA). Dr. Richard J. Nowak is supported by the NIH (award number U54‐NS115054).
ASJC Scopus subject areas
- General Neuroscience
- Clinical Neurology