Rare Skin Cancer Patient’s LEMS Symptoms Ease With Antibody Treatment

Rare Skin Cancer Patient’s LEMS Symptoms Ease With Antibody Treatment
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Treatment with immunoglobulins, or antibodies — proteins that help fight off infections — successfully reduced symptoms of Lambert-Eaton myasthenic syndrome (LEMS) in a woman receiving immunotherapy for a rare type of skin cancer.

Her case suggests that immunoglobulin therapy may prove an effective option for treating patients with paraneoplastic LEMS who are also receiving immunotherapy. Paraneoplastic LEMS occurs when the disease is triggered by an immune reaction to cancer.

Titled “Immunoglobulins to mitigate paraneoplastic Lambert Eaton Myasthenic Syndrome under checkpoint inhibition in Merkel cell carcinoma,” the case report was published in the journal Neurological Research and Practice.

The patient is a 62-year-old woman treated at the medical facility of Aachen University, in Germany, for drooping eyelids, trouble swallowing, muscle weakness, and fatigue.

A physical examination showed hand muscle weakness, while a neuromuscular evaluation revealed a decreased response to electrical stimulation in the muscles of her upper back and elbow.

A biochemical exam showed elevated blood levels of antibodies directed against P/Q-type voltage-gated calcium channels (VGCCs).

In healthy individuals, calcium prompts the release of the neurotransmitter acetylcholine via VGCCs, which leads to muscle contraction. In LEMS, antibodies against VGCCs block their function and the transmission of messages from the nerves to muscles.

This patient had not developed antibodies against acetylcholine receptors.

She began LEMS treatment with Firdapse (amifampridine) and pyridostigmine. The team also evaluated her for cancer, as an estimated 50% of LEMS cases arise from an underlying cancer.

Several suspicious lymph nodes were found using positron emission tomography (PET). These were later confirmed by biopsy to be caused by metastatic Merkel cell carcinoma. The link between LEMS and this type of cancer had already been reported.

Cancer becomes metastatic when tumor cells break away from the initial tumor to colonize other areas of the body. Although the attending physicians could tell that the patient’s nodes were metastases, they were unable to find the original tumor.

The woman’s cancer was treated with Bavencio (avelumab), an immune checkpoint inhibitor (ICI). Immune checkpoints are effectively “off” signals for T-cells, a type of immune cell responsible for killing infected cells. Cancer cells can evade the immune response by triggering this off switch effect. Bavencio specifically targets a protein called PD-L1 on tumor cells to make them susceptible to recognition by T-cells.

Treatment with Bavencio, however, led to a worsening of LEMS symptoms, such as limb weakness that made the patient require a walker, and to a severe reduction of the amount of air she could exhale after taking a deep breath (called vital capacity).

Because of her cancer’s severity, a medical board recommended against stopping Bavencio treatment entirely. Several other options were weighed but rejected, due to possible drug-drug interactions, the potential need for long-term therapy, or out of consideration for the patient’s underlying diabetes.

The physicians finally opted for immediate treatment with intravenous (into the vein) immunoglobulins, given at 2 g/kg body weight for five consecutive days.

The woman’s symptoms eased on this regimen and doctors kept her on immunoglobulin therapy at an intermittent dose of 1 g/kg body weight every four weeks.

The patient tolerated this treatment well and reported decreases in her symptoms. After six months, she was able to walk up to 500 meters and showed normal endurance of legs and arms.

Benefits also were found in the muscle response to electrical stimulation. In addition, she regained some of her vital capacity. However, her distal muscle strength, that of the muscles near the ends of her limbs, was still impaired.

Notably, her Merkel cell carcinoma had been in complete remission, at least to the time of this case report’s publication.

This patient is the first known case of Bavencio treatment and paraneoplastic LEMS. Her improvement following ICI therapy raises the possibility that this may prove a successful treatment strategy going forward.

“We conclude that immunoglobulins are a conceivable treatment option to control an ICI-associated deterioration of paraneoplastic symptoms,” they wrote.

Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Forest Ray received his PhD in systems biology from Columbia University, where he developed tools to match drug side effects to other diseases. He has since worked as a journalist and science writer, covering topics from rare diseases to the intersection between environmental science and social justice. He currently lives in Long Beach, California.
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