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Occupational and Environmental Lung Diseases · Journal article
Frontiers in Immunology · September 10, 2026
Encouraging direction, but not yet definitive.
Early dynamic changes in serum tumor markers and immune-inflammatory biomarkers on Day 21 of ICI therapy were associated with subsequent ICI-associated myasthenia gravis in NSCLC patients. A composite four-component score stratified risk from 1.2% to 6.7%, with moderate discriminatory performance (corrected AUROC 0.731), but external validation is required before clinical implementation.
Retrospective single-center cohort study with landmark analysis and internal bootstrap validation. Consecutive patients with NSCLC receiving first ICI-based therapy at a single center; baseline cohort n=826; Day-21 landmark cohort n=782. Intervention: ICI-based therapy (first exposure); serum biomarker assessment at baseline, Day 21, and Day 42. Compared with: Non-event patients (those not developing ICI-associated myasthenia gravis within 180 days). n = 826. Single center (location not specified in source).
Patients who developed ICI-associated myasthenia gravis showed greater Day-21 increases in cytokeratin 19 fragment antigen 21-1, carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, C-reactive protein, and lactate dehydrogenase, with larger albumin decline Day-21 dynamic score stratified event rates from 1.2% in low-risk group to 6.7% in high-risk group among 782 Day-21 cohort patients with 21 events after Day 21 Integrated Day-21 model achieved optimism-corrected area under the receiver operating characteristic curve of 0.731
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The Day-21 biomarker score may help clinicians identify NSCLC patients requiring closer neuromuscular and cardiac surveillance early in ICI therapy. However, external validation is required before adoption into clinical practice, and the rare event rate (3.3%) and single-center design limit immediate generalizability.
A single-center retrospective cohort study with moderate internal discrimination (AUROC 0.731 corrected) identifying early biomarker changes associated with rare ICI-induced myasthenia gravis; findings require external validation before clinical use.
As stated by the source record.
Quoted from the source exactly as published.
The Day-21 biomarker score may help clinicians identify NSCLC patients requiring closer neuromuscular and cardiac surveillance early in ICI therapy. However, external validation is required before adoption into clinical practice, and the rare event rate (3.3%) and single-center design limit immediate generalizability.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of non-small cell lung cancer (NSCLC), but immune-related neuromuscular toxicities remain difficult to anticipate. ICI-associated myasthenia gravis is uncommon, frequently occurs early after treatment initiation, and may overlap with myositis or myocarditis. Clinically accessible blood-based indicators that help identify patients entering this high-risk period remain insufficiently defined. Objective This study evaluated whether early dynamic changes in serum tumor markers and immune-inflammatory biomarkers could serve as noninvasive indicators of subsequent ICI-associated myasthenia gravis in patients with NSCLC. Methods Consecutive patients with NSCLC who received their first ICI-based therapy between 1 January 2018 and 31 January 2025 were retrospectively screened at a single center. Baseline, Day-21, and Day-42 laboratory windows were prespecified before endpoint modeling. Serum tumor markers included carcinoembryonic antigen, cytokeratin 19 fragment antigen 21-1, neuron-specific enolase, squamous cell carcinoma antigen, and carbohydrate antigen 125. Immune-inflammatory biomarkers included neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, C-reactive protein, lactate dehydrogenase, and albumin. The primary endpoint was definite or probable ICI-associated myasthenia gravis occurring within 180 days after first ICI exposure. Landmark models were developed using Firth bias-reduced logistic regression and internally validated by bootstrap resampling. The Day-21 dynamic score used clinically pragmatic thresholds defined before endpoint modeling. Results The final baseline cohort included 826 patients, of whom 27 developed definite or probable ICI-associated myasthenia gravis within 180 days. The Day-21 landmark cohort included 782 patients and 21 events occurring after Day 21. Compared with non-event patients, patients who later developed ICI-associated myasthenia gravis showed greater Day-21 increases in cytokeratin 19 fragment antigen 21-1, carcinoembryonic antigen, neutrophil-to-lymphocyte ratio, C-reactive protein, and lactate dehydrogenase, together with a larger decline in albumin. A four-component Day-21 dynamic score combining tumor-marker instability, neutrophil-to-lymphocyte ratio activation, C-reactive protein/lactate dehydrogenase flare, and albumin decline stratified event rates after Day 21 from 1.2% in the low-risk group to 6.7% in the high-risk group. The integrated Day-21 model achieved an apparent area under the receiver operating characteristic curve of 0.759 and an optimism-corrected area under the receiver operating characteristic curve of 0.731, indicating moderate internal discrimination. Conclusion Early dynamic changes in routine serum tumor markers and immune-inflammatory biomarkers were associated with increased risk of ICI-associated myasthenia gravis in patients with NSCLC. The Day-21 integrated biomarker score may help identify patients requiring closer neuromuscular and cardiac toxicity surveillance during the first few weeks of ICI therapy, but external validation is required before clinical implementation.
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