Cancer meds may trigger symptom worsening in some with LEMS
Use of immune-activating treatments require caution, cases show
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In certain people with Lambert-Eaton myasthenic syndrome (LEMS), medications called immune checkpoint inhibitors (ICIs) can be safely used to manage underlying lung cancers. In other cases, however, the use of ICIs — which have been shown to improve survival in some lung cancer patients — may trigger dangerous worsening of LEMS symptoms.
That’s according to a case series reporting on four people with LEMS associated with small-cell lung cancer (SCLC) who were treated with ICIs. The four had widely varying outcomes, the researchers noted.
The findings highlight that these therapies need to be deployed cautiously, the researchers say. The team called for further research to determine why some patients respond better than others, so that treatment can be better personalized to improve outcomes.
“The [varied] outcomes in this case series raise questions as to why some patients with pre-existing LEMS tolerate ICIs without complications whereas others experience flares,” the scientists wrote, adding that “further research is warranted to identify biomarkers or immune profiles that predict safe ICI use in patients with [LEMS].”
The study, “Immunotherapy in Patients With Small-Cell Lung Cancer and Lambert-Eaton Myasthenic Syndrome: A Multi-institutional Case Series,” was published in the journal Clinical Lung Cancer by scientists in the U.S. and Turkey.
LEMS is an autoimmune disease in which the immune system wrongly produces self-reactive antibodies that attack nerve cells responsible for motor control, resulting in symptoms such as muscle weakness.
In at least half of cases, LEMS develops in people with an underlying cancer. A specific type of cancer called SCLC, linked to smoking, underlies most cases of cancer-associated LEMS.
Cancer meds known as ICIs now approved in US, elsewhere
SCLC tumor cells often produce high levels of checkpoint molecules, which are signaling proteins that the body’s cells typically use to tell the immune system that they are not a threat. This way, tumor cells can hide from cancer-killing immune cells that would otherwise destroy them.
ICIs are a relatively new type of anticancer therapy that works by blocking the activity of checkpoint molecules, thereby unleashing the immune system to more effectively attack and destroy cancer cells. Several ICIs are approved in the U.S. and elsewhere to treat SCLC.
The use of ICIs in people with LEMS poses a conundrum, however. On the one hand, ICIs can activate the immune system to better destroy the tumor. But on the other hand, increased immune activity may trigger LEMS worsening. To date, there’s been little information reported on if or how ICIs can best be used to manage such cancers in LEMS patients.
“ICIs are essential components of [bodywide] therapy in SCLC and have led to improved survival,” the researchers wrote. “However, their use in patients with pre-existing neurological autoimmune diseases [such as LEMS] remains a subject of caution.”
In this report, the scientists detailed the cases of four people with SCLC-associated LEMS who received ICI treatment.
“Given the rarity of SCLC-associated LEMS and the exclusion of such patients from clinical trials, real-world case series provide important insights and highlight the need for additional long-term, … multicenter studies,” the researchers wrote.
[Immune checkpoint inhibitors] are essential components of [bodywide] therapy in [lung cancer] and have led to improved survival. … However, their use in patients with pre-existing neurological autoimmune diseases [such as LEMS] remains a subject of caution.
Two patients received an ICI therapy called durvalumab (sold as Imfinzi), while the other two were given atezolizumab (sold as Tecentriq, among others).
Specific regimens differed between the cases, but ICIs were generally given following first-line chemotherapy, according to the researchers. All four patients also received the approved LEMS treatment Firdapse (amifampridine) to manage LEMS symptoms, the team noted.
Worse LEMS seen for 2 of 4 patients
The four patients had very different experiences with ICI treatment.
In two cases — a 77-year-old woman given durvalumab and a 55-year-old man treated with atezolizumab — the use of ICI had little to no effect on LEMS symptoms. As of the latest follow-up, both patients had minimal muscle weakness and had achieved a complete response to cancer treatment, meaning there were no detectable signs of tumor. The man, the report noted, also had “near-complete” recovery of his neurological symptoms following treatment.
In the other two cases, both involving women age 65, ICIs appeared to trigger LEMS worsening.
In one of the women, the use of durvalumab led to worse LEMS symptoms, with new difficulty walking, despite a complete response in terms of cancer signs. This patient’s neurological symptoms eased considerably once she discontinued durvalumab and upped her dosage of LEMS medication. At the latest follow-up, she was able to walk with a cane and continued to show no signs of SCLC.
For the other woman, who was bedbound at the start of treatment, atezolizumab was given as part of her initial anticancer therapy. She also began taking Firdapse, and her symptoms rapidly lessened, allowing her to walk again without assistance.
However, after about four months, her symptoms worsened, and she became bedbound again, despite ongoing Firdapse treatment and no signs of cancer progression. She ultimately chose to stop cancer treatment and pursue hospice care; she died slightly longer than one year after her diagnosis.
The scientists said it’s not totally clear why these four patients had such different experiences with ICI treatment, and they called for further studies aimed at predicting ICI response in cancer-associated LEMS.
In the meantime, “close multidisciplinary monitoring is essential to balance oncologic benefit against neurologic risk” in people with SCLC-related LEMS, the team concluded.
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