Immune checkpoint inhibitor for cancer doesn’t affect woman’s LEMS
Case suggests that such inhibitors may be safe in select use for LEMS patients
For a woman with cancer complicated by Lambert-Eaton myasthenic syndrome (LEMS), treating the cancer with an immune checkpoint inhibitor did not worsen her LEMS, according to a report.
Her case suggests that, at least in some instances, immune checkpoint inhibitors may be a treatment option for cancer patients who also have LEMS, even though such use “is not strongly recommended and remains challenging,” the researchers wrote.
The report, “Durvalumab for Extensive-Stage of Small-Cell Lung Cancer With Lambert-Eaton Myasthenic Syndrome,” was published in the Journal of Medical Cases.
Inhibitor works to activate the immune system against cancer cells
LEMS is caused by the immune system erroneously attacking healthy nerve cells by making self-reactive antibodies targeting voltage-gated calcium channels (VGCCs). The resulting damage interferes with the nerves’ ability to communicate with muscles, ultimately causing muscle weakness and other disease symptoms.
Many cases of LEMS develop in people who have cancer, most commonly small-cell lung cancer. Immune checkpoint inhibitors, or ICIs, are a recently developed group of treatments that work by blocking signals that tumor cells use to avoid being targeted and destroyed by the immune system. By blocking these signals, ICIs make it easier for the immune system to destroy cancer cells.
While immune checkpoint inhibitors can be effective in treating cancer, activating the immune system can cause unwanted side effects. There have been reports of ICIs triggering the development of LEMS and other immune-mediated complications.
A pair of scientists at Osaka Police Hospital in Japan reported the case of a 62-year-old woman with both LEMS and small-cell lung cancer who successfully underwent ICI treatment.
Her early symptoms included leg weakness that caused trouble walking and led to falls. Other symptoms included drooping eyelids, dizziness, and abdominal pain. After a number of tests, she was diagnosed with both LEMS and cancer, and given pyridostigmine to help manage her muscle weakness.
Clinicians proposed two potential treatment plans to tackle her cancer: a round of chemotherapy given in combination with an ICI called durvalumab (sold under the brand name Imfinzi), or chemotherapy alone. Clinicians said that adding an ICI would likely be more effective for treating the cancer, but might worsen LEMS.
After discussing the potential benefits and risks, she ultimately decided on chemotherapy plus durvalumab. She underwent four rounds of triweekly treatment with a regimen of durvalumab and platinum-based chemotherapy. She responded to it well, with levels of tumor markers decreasing by about tenfold.
Two additional rounds of durvalumab were given as maintenance therapy, aiming to keep cancer growth suppressed. Throughout treatment, her LEMS did not worsen. Rather, while measures of nerve function didn’t change, her symptoms eased following treatment, which was accompanied by a decrease in the levels of anti-VGCC antibodies.
“The most important finding of our case was that four induction courses of durvalumab plus platinum-based chemotherapy and two additional courses of durvalumab maintenance did not exacerbate the preexisting LEMS,” the researchers wrote.
This finding shows that ICIs can be used to treat cancer patients with LEMS without worsening LEMS, at least in some cases, the scientists said. They stressed that it’s impossible to draw generalized conclusions from this single case, emphasizing the importance of working with patients to develop an individualized treatment plan.
After two rounds of maintenance therapy, imaging revealed that the patient’s cancer had spread to her brain, and she was started on radiation therapy and an anti-cancer medication called amrubicin.
At 1.5 years after her initial diagnosis, she was continuing treatment.