In first reported case, using efgartigimod helps manage LEMS
MG therapy shown to ease symptoms in 73-year-old man with cancer
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Lambert-Eaton myasthenic syndrome (LEMS) linked to an underlying lung cancer was successfully managed with four weekly intravenous, or into-the-vein, infusions of efgartigimod — a medication approved for treating myasthenia gravis (MG) — in an elderly man in China, according to a case report.
LEMS and MG are both autoimmune disorders of the neuromuscular junction, the site where specialized nerve cells called motor neurons communicate with muscle fibers. Standard MG therapies, such as pyridostigmine (sold as Mestinon, also available as generics), are sometimes used off-label to treat muscle weakness in LEMS.
Here, the man, 73, failed to respond to pyridostigmine, but experienced a reduction in disease-driving antibodies and symptoms after treatment with efgartigimod — sold as Vyvgart for certain MG patients.
“This is the first report on the use of efgartigimod in LEMS,” the researchers wrote. “The patient demonstrated substantial clinical improvement following treatment. Nevertheless, more clinical studies are required to verify whether efgartigimod offers a novel treatment approach for patients with LEMS.”
The study, “Case Report: A Patient with Lambert-Eaton Myasthenic Syndrome Successfully Treated with Efgartigimod,” was published in the International Medical Case Reports Journal.
LEMS occurs when self-reacting antibodies mistakenly target and damage voltage-gated calcium channels (VGCCs), a specific type of calcium channel protein at nerve cell endings. As a result, nerve cells release less acetylcholine, a chemical messenger that triggers muscle contraction, ultimately causing symptoms of muscle weakness.
In as many as 60% of cases, LEMS is associated with an underlying cancer, most commonly small cell lung cancer (SCLC), a rare and aggressive form of lung cancer. In such cases, the first-line treatment for LEMS is treating the underlying tumor.
LEMS treatment Firdapse not available in all countries
When the cancer cannot be effectively treated, or no tumor can be identified, additional therapies — such as the LEMS-approved medication Firdapse (amifampridine) — are needed to control symptoms, while corticosteroids are often used to suppress immune activity. According to the researchers, however, such treatments “may take effect slowly and some have unbearable side effects.”
Additionally, the team noted, Firdapse is not available in all countries, including China.
Efgartigimod, given directly into the bloodstream, accelerates the destruction of antibodies, including those that drive autoimmune diseases such as MG and LEMS. It works by blocking FcRn, a protein that normally prevents circulating antibodies from being destroyed. The approved treatment regimen in people with MG involves weekly infusions in four-week cycles.
Now, in what they believe is a first case, a team of researchers reported on a man with LEMS whose disease was successfully managed with efgartigimod.
The man had been diagnosed with SCLC in May 2023 and had received eight courses of chemotherapy. About a year later, he began developing neurological symptoms, including drooping eyelids, difficulty speaking and chewing, and trouble lifting his head. He also had weakness that was more pronounced in his legs, limiting his ability to stand and walk.
Three days of treatment with the corticosteroid methylprednisolone (at 40 mg per day) did not improve his condition. Further testing at the hospital supported a LEMS diagnosis.
Specifically, blood tests showed elevated levels of anti-VGCC antibodies, as well as antibodies against the SOX1 protein. This type of antibody is a marker for SCLC-related LEMS. Responses to repetitive nerve stimulation also showed an abnormal pattern often seen in the condition.
Additionally, scores on standard clinical scales used to assess muscle strength and daily functioning were high, indicating severe muscle weakness and significant functional impairment.
Improvements seen within 1 week of starting efgartigimod
The man’s corticosteroid dose was increased to 80 mg per day, and he was started on pyridostigmine, an MG-approved therapy that helps boost acetylcholine levels. However, his muscle weakness worsened, and he developed shortness of breath at rest. Clinical scores remained high.
On the fifth day of corticosteroid treatment, he received an infusion of 400 mg efgartigimod. Within a week, his condition clearly improved. He was able to sit independently, feed himself, brush his teeth, and lift his legs from the bed. Score changes in clinical scales also reflected improved muscle strength and greater independence in daily activities.
Three additional 400 mg doses of efgartigimod were given, each one week apart. By the fourth infusion, blood tests showed a marked drop in anti-VGCC antibody levels, and the man’s clinical scores dropped even further, indicating “a significant positive response to efgartigimod in this LEMS patient,” the team wrote.
One month after the fourth dose, a follow-up call found the man was managing daily activities well. However, more than a month after his final infusion, he died suddenly at home after experiencing chest and back pain.
We observed a significant improvement in the patient’s clinical symptoms and laboratory indicators. … Accordingly, [we suggest that] efgartigimod is an alternative … treatment for LEMS.
Because the man had previously developed a blood clot in a vein in his leg, the researchers hypothesized that he may have died from a pulmonary embolism — which occurs when a blood clot travels to the lungs and blocks blood flow — or from a heart-related event.
“Despite the unfortunate sudden death of our patient, we observed a significant improvement in the patient’s clinical symptoms and laboratory indicators,” the researchers wrote. “Accordingly, [we suggest that] efgartigimod is an alternative … treatment for LEMS.”
Still, larger studies are needed to confirm the therapy’s safety and efficacy in this patient population, according to the team.
