New data link LEMS to several cancer types, not just SCLC
Study also finds that symptoms improve with tumor-directed treatment
Written by |
Lambert-Eaton myasthenic syndrome (LEMS) can be caused by several types of cancer, not just the small-cell lung cancer (SCLC) that’s commonly associated with the immune system disease, according to new data from a European LEMS registry.
These data showed that, compared with autoimmune LEMS, which occurs on its own without a known cause, cancer-associated LEMS more often leads to ataxia, or problems with muscle coordination, among patients.
In addition, LEMS symptoms usually matched the cancer’s treatment status, improving when it was treated and worsening when it progressed.
“The frequent improvement of symptoms with tumor-directed treatment supports extended screening beyond SCLC and timely management,” the researchers wrote.
The study, “Paraneoplastic Lambert-Eaton myasthenic syndrome associated with non-small cell lung cancer: data from the European LEMS registry and systematic review,” was published in the journal Neurological Research and Practice. Two of the authors work at Serb Pharmaceuticals, which now holds the commercial rights of Firdapse (amifampridine), a LEMS-approved therapy.
LEMS occurs when self-reactive antibodies mistakenly attack certain proteins on nerve cells that control muscle movement. As a result, muscles do not receive normal signals from nerve cells instructing them to contract, ultimately leading to symptoms such as muscle weakness and fatigue.
Link to cancer seen in over half of LEMS cases
While LEMS can occur on its own, it is associated with cancer in more than half of cases. In these patients, the condition is then known as paraneoplastic LEMS or pLEMS. Although other types of cancer have been associated with LEMS, it most commonly occurs secondary to an aggressive type of lung cancer called small-cell lung cancer, or, for short, SCLC.
Now, a team led by researchers from Charité-Universitätsmedizin Berlin in Germany sought to compare LEMS associated with non-SCLC cancer with LEMS occurring secondary to SCLC and autoimmune LEMS. The scientists drew on data from the European LEMS registry, which was originally funded by Biomarin International, Firdapse’s original developer, to collect standardized clinical data from people with the disease.
Among the patients in the registry were 72 people with autoimmune LEMS, 12 with pLEMS associated with SCLC, and 11 with pLEMS associated with other types of cancer. The other cancer types included Merkel cell carcinoma, a rare and aggressive type of skin cancer, cancer of the thymus gland, and breast cancer. Some patients had lymphoproliferative disorders, which include benign and malignant blood cancers.
LEMS symptoms appeared before the cancer was diagnosed in 33% of cases of pLEMS associated with SCLC and 30% of those linked to other types of cancer. In the remaining patients, LEMS occurred at the same time as the cancer was diagnosed or afterward. Overall, the data showed that the timing can vary widely.
People with autoimmune LEMS were significantly younger at symptom onset than those with SCLC-related pLEMS (median of 56 vs. 64). Individuals with non-SCLC-related pLEMS were more often male (73%) relative to those with SCLC-pLEMS (42%) and those with autoimmune LEMS (50%).
Findings suggest cancer control is key to symptom severity
Ataxia was significantly more common in people with pLEMS, regardless of whether it was associated with SCLC or other types of cancer (64% and 55%), than in those with autoimmune LEMS (19%).
The severity of symptoms was measured using the Quantitative Myasthenia Gravis (QMG) scale, in which higher scores indicate more severe muscle weakness. At entry into the registry, participants with SCLC-related pLEMS scored about twice as high on the QMG scale as those in the other two groups.
However, the SCLC-related pLEMS group had started treatment for their cancer more recently, a median of three months before, “which likely contributed to the higher scores,” the team wrote.
Most people with non-SCLC-related pLEMS had already undergone longer treatment or completed their treatment, the data showed.
Nearly all patients (95%) received Firdapse or a similar treatment to manage their LEMS, but muscle strength generally improved when cancer treatment was effective and worsened if the cancer came back or progressed.
After cancer treatment was completed, LEMS symptoms were similar in severity across all three groups, the researchers noted. Those findings suggest that cancer control is key to symptom severity.
Expanding awareness of LEMS in non-SCLC tumors … has grown in recent years. … Timely recognition [of the cancer is key].
When reviewing published literature up to 2024, the researchers identified 115 additional cases of LEMS linked to cancer, the most common being non-SCLC (18%), followed by Merkel cell carcinoma (13%), and lymphoproliferative disorders (11%).
Most patients with outcome data (88%) improved after undergoing cancer treatment, which further supports the idea that cancer of any type can trigger LEMS, according to the researchers.
According to the researchers, “expanding awareness of LEMS in non-SCLC tumors … has grown in recent years.” The team concluded that “timely recognition” of the cancer is key, and also noted that “ataxia may serve as [a] red flag for pLEMS.”
Overall, the findings show that “early diagnosis of all pLEMS is essential to ensure timely treatment and ultimately improve patient outcomes,” the researchers wrote.
