Cancer Immunotherapy Tecentriq Tied to Higher LEMS Risk in Study

The immune checkpoint inhibitor is used to treat various cancers, including SCLC

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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People with small cell lung cancer (SCLC) treated with the immune-based cancer therapy atezolizumab are at an increased risk of developing Lambert-Eaton myasthenic syndrome (LEMS), according to a database analysis of adverse events.

The analysis was detailed in a study, “Increased risk of Lambert-Eaton myasthenic syndrome (LEMS) in small cell lung cancer patients treated with immune checkpoint inhibitor,” published as a letter to the editor in the European Journal of Cancer.

LEMS is a rare disease marked by muscle weakness caused by a self-directed immune attack on certain molecules found in nerve endings that control muscle movement. The disease can be associated with an underlying cancer, most commonly SCLC.

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What are immune checkpoint inhibitors?

Immune checkpoint inhibitors (ICIs), a form of immunotherapy, are widely used to treat various types of cancer, including SCLC. ICIs block cell surface proteins that prevent the immune system from identifying and destroying cancer cells.

However, because ICIs enhance the activity of the immune system, they often cause immune-related adverse events. In addition, autoimmune diseases like LEMS have been reported in cancer patients treated with ICIs.

To assess the risk of LEMS in SCLC patients undergoing ICI treatment, researchers in Japan examined the Japanese Adverse Drug Event Report database.

Adverse event reports associated with two ICIs — atezolizumab (sold under the brand name Tecentriq) and durvalumab (sold under the brand name Imfinzi) — both approved for SCLC in Japan, were evaluated. Outcomes were compared with other ICIs also approved in Japan, but not for SCLC.

The team identified 3,873 patients treated with atezolizumab, of whom 714 had SCLC (18.4%). Durvalumab was prescribed to 2,168 patients, including 263 with SCLC (12.1%).

There were 11 cases of LEMS among 764,653 adverse event reports not associated with an ICI, meaning an occurrence of 0.0014%. In contrast, six cases of LEMS were found among the 3,873 patients treated with atezolizumab for a prevalence of 0.15% — more than 100 times higher.

Our results suggest that SCLC patients who receive atezolizumab are at increased risk of LEMS

All six of these LEMS cases occurred in men with SCLC, five of them in their 70s, with symptoms easing after atezolizumab was stopped (in four cases for which outcome data were available).

The researchers noted that atezolizumab is more frequently associated with immune-related inflammation of the brain (encephalitis) compared with other ICIs, which “may be relevant to our results.”

No reports of LEMS were found among the 2,168 patients treated with durvalumab. Moreover, the occurrence of LEMS in patients treated with other ICIs approved for different cancer indications was similar to that seen in those without ICI exposure.

“Our results suggest that SCLC patients who receive atezolizumab are at increased risk of LEMS,” the researchers wrote.