Abstract

Objective: This study aimed to characterize adverse drug reactions (ADRs) associated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in cancer immunotherapy, identifying demographic, pharmacological, and clinical determinants of toxicity severity using real-world pharmacovigilance data.
Materials and methods: We analyzed 93,925 ADR reports from the FDA Adverse Event Reporting System (FAERS, 2023-2024). Data preprocessing included deduplication, terminology standardization, and severity classification. Multivariate logistic regression and machine learning models were employed to assess predictors of serious ADRs, integrating demographic variables (age, sex), drug agents, and organ-specific toxicities. Results: Pembrolizumab (38.4%), atezolizumab (26.5%), and nivolumab (25.0%) accounted for 89.9% of ADR cases. Frequent ADRs included death (7.9%), off-label use (7.5%), and malignant progression (6.9%). Immune-related toxicities (diarrhea, hypothyroidism, pneumonitis) comprised 6.1 – 2.4% of cases. Severe ADRs (grade 3 – 4) predominantly affected hepatic (68%), cardiac (65%), and neurological systems (62%). Octogenarians exhibited a 42% increased risk of serious ADRs (p < 0.001), with males representing 51.1% of severe cases (p < 0.001).
Conclusion: Age, sex, and drug-specific profiles critically influence PD-1/PD-L1 inhibitor toxicity. The findings support personalized risk stratification and time-dependent monitoring protocols to mitigate immune-related adverse events, particularly in elderly and male patients. These insights enhance evidence-based management strategies for optimizing immunotherapy safety.

Author Details

Authors

• Saizhu He^{1, 2}
• Jingyi Chen¹
• Liming Gu¹
• Weiqiang Zeng¹
• Ting Li¹
• Wenchang Zhao²

Departments

• ¹ Shunde Women and Children’s Hospital of Guangdong Medical University, Foshan, Guangdong, and
• ² School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, China

Address

Dr. Wenchang Zhao
School of Pharmacy
Guangdong Medical University
Dongguan, Guangdong, 523808, China
Email: [email protected]

Citation