Düsseldorf, Germany – A recent case report from Germany highlights the potential of blinatumomab, a cancer therapy, in treating refractory generalized myasthenia gravis (gMG)— a form of the autoimmune disease that does not respond to standard treatments. Two women with severe, treatment-resistant MG experienced marked clinical improvements following treatment with blinatumomab, suggesting it could offer a novel approach for managing difficult autoimmune conditions.
Published in Molecular Therapy, the report is titled “CD19xCD3 T cell engager blinatumomab effective in refractory generalized myasthenic syndromes.” Despite the encouraging outcomes, researchers emphasized caution: “Since this first-in-human experience comprises two cases, our findings should be viewed as proof-of-concept rather than evidence of broad clinical efficacy.” They noted the need for further studies to evaluate long-term effectiveness, safety, and underlying mechanisms.
Background on MG and Refractory Cases
Myasthenia gravis occurs when the immune system produces antibodies that interfere with communication between nerves and muscles, causing progressive muscle weakness, particularly with exertion. While many patients respond well to immunosuppressants, intravenous immunoglobulins, or newer biologics, a subset remains resistant to treatment—classified as refractory MG.
Patient Profiles and Prior Treatments
The two patients described in the report had long-standing, severe MG unresponsive to numerous therapies:
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Patient 1, a 41-year-old woman, was diagnosed in August 2020. Despite receiving corticosteroids, plasma exchange, intravenous immunoglobulin, rituximab, and newer agents like zilucoplan (Zilbrysq), she remained severely impaired, with difficulty breathing and moving.
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Patient 2, a 60-year-old woman, was diagnosed in October 2021 with anti-acetylcholine receptor antibody-positive MG. She also had Lambert-Eaton myasthenic syndrome (LEMS), another autoimmune neuromuscular disorder. Like Patient 1, she had experienced repeated myasthenic crises and failed to respond to standard therapies.
Blinatumomab Treatment Protocol
Each patient received two 12-day cycles of continuous intravenous blinatumomab, with a higher dose during the second cycle. Immunosuppressants were paused beforehand. Both women were pretreated with corticosteroids and paracetamol to reduce the risk of cytokine release syndrome (CRS), an inflammatory side effect.
Blinatumomab, sold under the brand name Blincyto, is approved for treating certain types of leukemia. It functions as a bispecific T-cell engager (BiTE) that brings T-cells into close proximity with CD19-expressing B-cells, which produce disease-driving antibodies, allowing the T-cells to eliminate them. It is thought to act more rapidly and thoroughly than agents like rituximab and does not require the immune system to do the killing.
Clinical Improvements and Biomarker Changes
Both patients showed rapid and sustained clinical improvement. Scores on standardized MG assessment tools decreased significantly:
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In Patient 1, the MG Activities of Daily Living (MG-ADL) score dropped by 4 points after the first cycle; the Quantitative MG (QMG) score fell from 27 to 18 within one month, with continued improvement over three months.
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In Patient 2, the MG-ADL score dropped by 3 points, and the QMG score fell from 19 to 8 after one month, stabilizing at 7 after three months.
Both patients also demonstrated increased mobility, reflected by higher daily step counts tracked via smartwatches.
Immune profiling showed divergent responses:
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Patient 1 maintained low B-cell levels, corresponding with sustained clinical gains.
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Patient 2 experienced a rebound in B-cell counts after three months, but her antibody levels declined and clinical condition continued to improve, possibly indicating that newly generated B-cells were not pathogenic.
Interestingly, one patient also reported improvement in skin and joint symptoms, suggesting that blinatumomab’s effects may extend beyond muscle-related manifestations of autoimmunity.
Side Effects and Safety
Both women experienced mild cytokine release syndrome, presenting as fever, fatigue, and headache. One also reported brief diarrhea and worsening of a pre-existing tachycardia (elevated heart rate) during the first cycle. No serious adverse events occurred.
Future Implications
Blinatumomab may offer a new therapeutic mechanism in MG by targeting and eliminating long-lived, antibody-producing B-cells that resist other forms of treatment. Unlike immune cell therapies, it does not require chemotherapy, cellular modification, or long preparation times, making it potentially more accessible.
However, the report’s findings are based on only two patients, both women, with different MG subtypes and treatment histories. The authors caution that results cannot yet be generalized. Larger, randomized controlled trials are essential to confirm these early results, determine optimal dosing, and better understand the drug’s mechanism in MG.
Contact
Prof. Dr. Tobias Ruck – University of Düsseldorf
Email [email protected]