A retrospective study showed that Lambert-Eaton myasthenic syndrome (LEMS) associated with small cell lung cancer (SCLC) may be underdiagnosed in real-world treatment settings, according to findings published in Frontiers in Oncology.1
What did the retrospective study show about LEMS in SCLC?
Of 867,170 patients with eligible lung cancer claims from 2017 to 2022, 46,995 (5.4%) who were presumed to have SCLC had claims for treatment containing etoposide and platinum. Of this population, 77 (0.16%; 95% CI, 0.13%-0.20%) had a claim for LEMS during the study period, and of 8513 patients with presumed SCLC and at least 12 months of follow-up, 16 (0.19%; 95% CI, 0.10%-0.28%) had a LEMS claim.
Among 76 patients with SCLC and LEMS diagnoses in the primary population and at least 12 months of claims history, the median time between diagnoses was 37 days (IQR, 1-155), and 19 (25%) had LEMS claims preceding lung cancer claims, most of whom (84%) had a lung cancer diagnosis within 90 days. When comparing the incidence of LEMS before and after the standardization of immune checkpoint inhibitor use in SCLC care based on a cutoff of March 2019, the prevalence rates were 0.15% and 0.18%, respectively (P = .49).
“Because diagnostic challenges prolong the time to LEMS diagnosis in both tumor- and non-tumor LEMS [populations], it becomes clear that LEMS diagnoses may be missed altogether. Indeed, fewer than half of patients with available information in our study were diagnosed with LEMS by a neurologist. When LEMS diagnoses followed SCLC diagnoses, the diagnosis was even less likely to be made by a neurologist relative to LEMS diagnoses preceding SCLC diagnosis, reflecting the opportunities for oncologists to recognize and confirm the condition,” Benjamin Drapkin, MD, PhD, an assistant professor in the Department of Internal Medicine at UT Southwestern Medical Center, wrote with coauthors in the publication.1 “[I]n a large, representative, and contemporary real-world population, over 90% of SCLC-associated LEMS cases appear to go undetected. This marked underdiagnosis occurs despite availability of effective LEMS treatment that can improve patients’ quality of life.”
What is LEMS, and how is it related to SCLC?
The study investigators described LEMS as an autoimmune neurologic disorder and a paraneoplastic complication of SCLC. Clinical hallmarks of LEMS include proximal muscle weakness, autonomic dysfunction, and areflexia, which may be misattributed to cancer or cancer-directed therapy, or go undetected entirely. The subtle presentation of LEMS in the confounding presence of SCLC, the authors noted, may heighten the risk of missed or delayed diagnosis.
How was the real-world LEMS study designed?
Investigators conducted a retrospective analysis of patient-level data collected from Symphony Health’s PatientSource database, which included medical and pharmacy health care claims for more than 300 million individuals in the US. Extracts for oncology were restricted to October 2017 to April 2022, and LEMS data were restricted to March 2014 to July 2022 for the analysis. Investigators collected information on patient age, sex, insurance type, and geographic area.
The primary outcome involved identifying LEMS claims among patients with lung cancer claims between 2017 and 2022 who also received etoposide plus platinum-based chemotherapy. Sensitivity analyses were also conducted by modifying the claims-based approach to include LEMS diagnoses based on a single LEMS claim and at least 3 LEMS claims spanning for 90 days or longer.
Across the primary sample, in cases without LEMS (n = 46,918) and with LEMS (n = 77), the mean age was 66.3 years and 64.5 years, respectively. Most patients in each population had commercial insurance (52.0% vs 62.3%) and resided in the South (44.8% vs 42.9%). Of note, patients with LEMS and lung cancer (n = 390) were significantly older (mean, 65.7 years) than those with LEMS without lung cancer (n = 1446; mean, 58.7 years; P <.001).
In August 2025, the NCCN updated its Clinical Practice Guidelines in Oncology for SCLC to include testing for LEMS.2,3
References
- Drapkin BJ, Morrell DJ, Grebla R, Shechter G, Gerber DE. Marked under-diagnosis of Lambert-Eaton myasthenic syndrome in small cell lung cancer: an analysis of real-world claims data. Front Oncol. Front Oncol. 2025;15:1650373. doi:10.3389/fonc.2025.1650373
- Lambert Eaton myasthenic syndrome (LEMS) antibody testing and treatment recommendations added to NCCN Clinical Practice Guidelines for small cell lung cancer (SCLC). News release. Catalyst Pharmaceuticals. August 6, 2025. Accessed August 31, 2026. https://tinyurl.com/y35jr9ww
- NCCN. Clinical Practice Guidelines in Oncology. Small cell lung cancer, version 1.2026. Accessed August 31, 2026. https://tinyurl.com/yfxv8b5b
