CAR T-Cell Therapy Shows Promise in Refractory Myasthenia Gravis, Evidence Still Limited

An estimated 10% to 20% of people with myasthenia gravis (MG) responded poorly to standard immunotherapies, leaving them with limited and frequently burdensome options. However, a cell therapy first developed for blood cancers has emerged as a candidate to fill this gap.

An invited review published in Muscle & Nerve examined the emerging use of chimeric antigen receptor (CAR) T-cell therapy in MG, drawing on preclinical work, case reports, and case series to weigh early efficacy signals against safety.¹ The authors reported consistent clinical improvement across a small pooled population while cautioning that larger trials would be needed to confirm it.

Why Refractory Disease Created an Unmet Need

MG was characterized as an autoantibody-mediated disorder in which antibodies target components of the neuromuscular junction, including the acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and lipoprotein receptor-related protein 4. Because autoreactive B cells and plasma cells sustained that antibody production, B-cell–directed treatment had become a primary therapeutic strategy, though existing antibodies often failed to reach every pathogenic B-cell population.

The stakes of incomplete control were documented in a retrospective Austrian cohort, in which 14 of 126 patients with generalized MG (11.1%) met strict criteria for treatment-refractory disease.² Those patients experienced more frequent exacerbations, more often required rescue treatments or escalated immunosuppression, and remained more severely affected at last follow-up, a burden that helped explain the search for therapies capable of deeper and more durable B-cell depletion.

What the Pooled Case Data Showed

Across 5 independent reports, 7 patients received CAR T cells directed at CD19, B-cell maturation antigen (BCMA), or both, and each showed clinical improvement.¹ Peak CAR T-cell expansion occurred between days 8 and 22 after infusion, most often near days 10 to 16, and measurable cell persistence ranged from 28 to roughly 180 days, although those values reflected the last recorded measurements rather than defined end points.

The reported patients were predominantly women and ranged in age from 33 to 64 years. Most carried anti-AChR antibodies, 1 carried anti-MuSK antibodies, and documented comorbidities included Lambert-Eaton myasthenic syndrome, rheumatoid arthritis, and thymoma.

The largest single experience came from the MG-001 trial (NCT04146051), a multicenter phase 1b/2a study of the RNA-engineered anti-BCMA product Descartes-08 in 14 patients with generalized MG. That study applied standardized manufacturing and uniform dosing without lymphodepleting chemotherapy and recorded meaningful gains across the MG-Activities of Daily Living, Quantitative MG, MG Composite, and MG Quality of Life 15-item Revised scales. Extended follow-up showed sustained benefit for up to 9 to 12 months in most patients who received 6 weekly infusions, and waning responses were recaptured on retreatment rather than reflecting cumulative toxicity.

Safety across the case reports appeared more favorable than in cancer applications. Adverse events consisted mainly of grade 1 to 2 cytokine release syndrome, with rare immune effector cell–associated neurotoxicity and mild hematologic effects, and no severe or life-threatening events were reported. In the MG-001 cohort, investigators recorded no cytokine release syndrome, neurotoxicity, prolonged cytopenias, or serious infections, alongside preserved immunoglobulin levels and maintained vaccine titers.

Study Limitations and the Trials Ahead

The authors were direct about the limits of the evidence. All efficacy data came from small, uncontrolled case reports and series, and the absence of control groups precluded firm conclusions about treatment effects. Systematic follow-up beyond 6 months was lacking, definitions of refractory disease varied across reports, and prior treatment exposure differed between patients, which constrained inferences about where CAR T-cell therapy belonged in the treatment sequence. No evidence-based criteria for patient selection could be derived.

Seven registered trials enrolling more than 260 participants were expected to conclude between 2026 and 2029, and the authors framed those results as decisive for questions of durability, comparative efficacy, and long-term safety. Until then, they wrote, CAR T-cell therapy in MG "should be regarded as an experimental, hypothesis-generating approach rather than a standard of care."

References

1. Hegelmaier T, Duscha A, Desel C, et al. Chimeric antigen receptor T-cells in myasthenia gravis: advances, safety challenges, and future directions. Muscle Nerve. 2026;73(6):942-951. doi:10.1002/mus.70222
2. Raht J, Brunner I, Tomschik M, et al. Frequency and clinical features of treatment-refractory myasthenia gravis. J Neurol. 2020;267(4):1004-1011. doi:10.1007/s00415-019-09667-5. doi:10.1007/s00415-019-09667-5