Association Between Serum 25-Hydroxyvitamin D Levels and Immune-Related Adverse Events During PD-1/PD-L1 Inhibitor Therapy: A Retrospective Study.
- 1College of Pharmaceutical Sciences, Changxing People's Hospital, Zhejiang Chinese Medical University, Huzhou, Zhejiang, People's Republic of China.
- 2Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou, Huzhou, People's Republic of China.
- 3Department of Pulmonary and Critical Care Medicine, Changxing People's Hospital, Zhejiang Chinese Medical University, Huzhou, Zhejiang, People's Republic of China.
Abstract
Purpose
Vitamin D exerts pleiotropic immunomodulatory effects, yet its relationship with immune-related adverse events (irAEs) during PD-1/PD-L1 inhibitor therapy remains unclear. We examined the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and documented irAEs in a real-world cohort.Patients and methods
In this single-center retrospective study, we analyzed 46 serum 25(OH)D test records from 35 patients treated with PD-1/PD-L1 inhibitors between October 2023 and April 2026; lung cancer was the predominant tumor type. Documented irAEs were adverse events recorded in the dataset, adjudicated as immunotherapy-related by the treating clinicians and graded according to CTCAE version 5.0. Vitamin D status was classified as deficient (<30 nmol/L), insufficient (30 to <50 nmol/L), or sufficient (≥50 nmol/L). Because repeated records from the same patient are not statistically independent, record-level analyses were treated as exploratory, whereas the primary analysis was performed at the patient level using each patient's first available 25(OH)D measurement to ensure independence of observations.Results
Eleven record-level irAEs were documented in 9 patients; after exclusion of one event with unverifiable immune-mediated attribution (isolated hypokalemia), 8 patients had adjudicated irAEs in the primary analysis. At the exploratry record level, irAE proportions decreased stepwise across vitamin D categories: 60.0% (deficient), 20.0% (insufficient), and 6.3% (sufficient) (Cochran-Armitage trend, P=0.003). In the primary patient-level analysis, proportions were 62.5%, 13.3%, and 8.3%, respectively (trend P=0.008); first-test 25(OH)D concentrations were lower in patients with irAEs than in those without (median 26.70 vs 45.50 nmol/L; P=0.007), although the binary comparison (deficient/insufficient vs sufficient) was not statistically significant (P=0.216; OR=4.813, 95% CI: 0.517-44.824). In 10 of the 11 event-positive records, the documented event preceded the linked vitamin D measurement.Conclusion
Lower serum 25(OH)D concentrations were associated with documented irAEs in this small exploratory dataset. Given the temporal ambiguity and residual confounding, the findings are hypothesis-generating and cannot establish causality or prediction; whether vitamin D status can help risk-stratify patients for irAEs-rather than merely reflecting immune activation or nutritional status-requires prospective studies with protocol-defined pretreatment sampling.
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BibTeX
@article{zhang2026association,
title = {{Association Between Serum 25-Hydroxyvitamin D Levels and Immune-Related Adverse Events During PD-1/PD-L1 Inhibitor Therapy: A Retrospective Study.}},
author = {Yue Zhang and Peng Zeng and Weibin Fan and Bin Lin and Jing Fan},
journal = {Drug design, development and therapy},
year = {2026},
month = oct,
doi = {10.2147/dddt.s654669},
url = {https://europepmc.org/article/MED/42928853},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Association Between Serum 25-Hydroxyvitamin D Levels and Immune-Related Adverse Events During PD-1/PD-L1 Inhibitor Therapy: A Retrospective Study.
AU - Yue Zhang
AU - Peng Zeng
AU - Weibin Fan
AU - Bin Lin
AU - Jing Fan
PY - 2026
DA - 2026/10/21
JO - Drug design, development and therapy
DO - 10.2147/dddt.s654669
UR - https://europepmc.org/article/MED/42928853
AB - Purpose Vitamin D exerts pleiotropic immunomodulatory effects, yet its relationship with immune-related adverse events (irAEs) during PD-1/PD-L1 inhibitor therapy remains unclear. We examined the association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and documented irAEs in a real-world cohort.Patients and methods In this single-center retrospective study, we analyzed 46 serum 25(OH)D test records from 35 patients treated with PD-1/PD-L1 inhibitors between October 2023 and April 2026; lung cancer was the predominant tumor type. Documented irAEs were adverse events recorded in the dataset, adjudicated as immunotherapy-related by the treating clinicians and graded according to CTCAE version 5.0. Vitamin D status was classified as deficient (<30 nmol/L), insufficient (30 to <50 nmol/L), or sufficient (≥50 nmol/L). Because repeated records from the same patient are not statistically independent, record-level analyses were treated as exploratory, whereas the primary analysis was performed at the patient level using each patient's first available 25(OH)D measurement to ensure independence of observations.Results Eleven record-level irAEs were documented in 9 patients; after exclusion of one event with unverifiable immune-mediated attribution (isolated hypokalemia), 8 patients had adjudicated irAEs in the primary analysis. At the exploratry record level, irAE proportions decreased stepwise across vitamin D categories: 60.0% (deficient), 20.0% (insufficient), and 6.3% (sufficient) (Cochran-Armitage trend, P=0.003). In the primary patient-level analysis, proportions were 62.5%, 13.3%, and 8.3%, respectively (trend P=0.008); first-test 25(OH)D concentrations were lower in patients with irAEs than in those without (median 26.70 vs 45.50 nmol/L; P=0.007), although the binary comparison (deficient/insufficient vs sufficient) was not statistically significant (P=0.216; OR=4.813, 95% CI: 0.517-44.824). In 10 of the 11 event-positive records, the documented event preceded the linked vitamin D measurement.Conclusion Lower serum 25(OH)D concentrations were associated with documented irAEs in this small exploratory dataset. Given the temporal ambiguity and residual confounding, the findings are hypothesis-generating and cannot establish causality or prediction; whether vitamin D status can help risk-stratify patients for irAEs-rather than merely reflecting immune activation or nutritional status-requires prospective studies with protocol-defined pretreatment sampling.
SN - 1177-8881
ER -