Teclistamab Shows Rapid Efficacy in Two Patients with Autoimmune Neuropathy in Landmark Compassionate Use Report
核心洞察
An interdisciplinary team at Jena University Hospital administered the multiple myeloma (搜索) drug teclistamab to two patients with an autoimmune peripheral nervous system disorder (搜索) in a compassionate use setting.
Both patients received four injections over six weeks and showed rapid, significant improvement, with causative IgM (搜索) antibodies and paraproteins becoming undetectable in the blood shortly after treatment.
Nerve function recovered significantly, with previously unresponsive nerves becoming electrically detectable again on electroneurography, and neither patient experienced severe side effects over more than one year of follow-up.
An interdisciplinary team at Jena University Hospital has reported a surprisingly rapid and significant improvement in two patients with an autoimmune peripheral nervous system disorder (搜索) following treatment with teclistamab, a bispecific T-cell engager originally developed for multiple myeloma (搜索). The findings, published in Nature Communications, represent a novel therapeutic approach for a condition that currently lacks any approved disease-modifying treatment.
The disease, triggered by a malfunction of the immune system, leads to massive production of IgM (搜索) antibodies that attack the myelin sheaths enveloping peripheral nerves. As these sheaths degrade, they can no longer support signal transmission or protect and nourish nerve fibers, impairing nerve impulse conduction and eventually causing nerve cell death. Patients typically experience a progressive course beginning with tingling and numbness in the fingers and feet, advancing to tremors, balance issues, and severely restricted mobility.
Unmet Need and Treatment Rationale
Currently, no approved treatment targets the underlying cause of this autoimmune neuropathy. Corticosteroids and other immunosuppressive agents are used to manage symptoms, while plasmapheresis can temporarily reduce pathogenic antibody levels in the blood. However, for the two patients treated at Jena's specialized neuroimmunology clinic, these measures yielded only minimal and short-lived benefits. One patient had reached a point where she could only walk short distances with bilateral support, and climbing stairs was nearly impossible. The second patient had an even longer disease history with similarly poor outcomes.
Dr. Jonathan Wickel and Dr. Mihai Ceanga, the patients' attending physicians, hypothesized that teclistamab could address the root cause of the disease. In multiple myeloma (搜索), the drug directs T-cells to abnormal plasma cells for destruction. Since the pathogenic IgM (搜索) antibodies driving the neuropathy are also produced by plasma cells, the neurologists reasoned that eliminating these antibody-producing cells could halt the autoimmune attack on peripheral nerves.
Clinical Outcomes
In a compassionate use setting, the two patients received four injections of teclistamab over a six-week period. Both demonstrated rapid and clinically meaningful improvement. Within weeks, the patients were able to walk considerably more confidently and over longer distances.
Monthly clinical and laboratory examinations documented the treatment effect. "The causative IgM (搜索) antibodies and paraproteins were no longer detectable in the blood after only a short time. We also found fewer neurofilaments, which enter the bloodstream as fragments during the breakdown of nerve cells," said Dr. Jonathan Wickel. Ultrasound scans confirmed a reduction in inflammatory processes affecting the nerves.
Electrophysiological assessments revealed striking recovery. Dr. Mihai Ceanga noted: "Some nerves that had shown no measurable response at all during pre-treatment electroneurography became electrically detectable again. Overall, nerve conduction recovered significantly."
Importantly, neither patient has experienced any severe side effects since the treatment, now more than one year post-administration.
Expert Assessment and Next Steps
Prof. Dr. Christian Geis, Director of the Department of Neurology at Jena University Hospital, assessed the findings: "These two cases prove that modern cancer immunotherapies may also be effective in treating autoimmune diseases. In this instance, we were able to specifically target the antibody-producing cells rather than merely treating the consequences of the autoimmune reaction. Clinical trials are now required to substantiate the safety and efficacy of this treatment approach."
The case report, published as Wickel, J., Ceanga, M., Vlad, B. et al. in Nature Communications (2026), provides proof-of-concept that T-cell engaging therapies may have broader applications beyond oncology, potentially opening a new therapeutic avenue for antibody-mediated autoimmune neurological disorders.