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Cancer Site and Adverse Events Induced by Immune Checkpoint Inhibitors: A Retrospective Analysis of Real-life
Ammar Sukari1, Misako Nagasaka2,3, Roba Alhasan4
1Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, U.S.A. sukaria@karmanos.org.
Background:
Data on the characteristics of patients who are likely to experience adverse events, both immune-related and non-immune-related, from programmed cell death-1 (PD1) inhibitors are limited.
Patients And Methods:
Data from patients who received ≥1 dose of single-agent PD1 inhibitor between August 3, 2011 and August 31, 2016 were obtained from our Institution's pharmacy database. AEs were graded using Common Terminology Criteria for Adverse Events version 4.
Results:
One hundred and eighty-two patients received at least one dose of single-agent PD1 inhibitor prior to data cut-off. After excluding 14 patients with uncommon malignancies, the total number of patients were 168. The median age was 63 (range=24-92) years. There were 87 (52%) cases of non-small cell lung cancer (NSCLC), 35 (21%) of renal cell carcinoma (RCC), 12 (7%) of melanoma, 18 (11%) of Hodgkin's lymphomas, eight (5%) of head and neck squamous cell carcinoma (HNSCC) and eight (5%) of small cell lung cancer. Considering grade 2 or more AEs, 30 (18%) patients had kidney injury, 34 (20%) hypothyroidism, 36 (21%) transaminitis, 20 (12%) pneumonitis, and 18 (11%) colitis. Patients with RCC had higher odds of experiencing grade 2 or more kidney injury than patients with other primary tumor types (adjusted p=0.025), whereas patients with Hodgkin's lymphoma and HNSCC had higher odds of grade 2 hypothyroidism (adjusted p=0.005). Patients with NSCLC had higher risk of death with pneumonitis than those whose primary cancer was not NSCLC (adjusted p=0.005).
Discussion:
The increased odds of patients with Hodgkin's lymphoma and HNSCC experiencing grade 2 or more hypothyroidism may be related to previous radiation exposure. Most patients with RCC had undergone nephrectomy, making them more susceptible to acute kidney injury. When pneumonitis occurred in patients with primary NSCLC, the overall survival was significantly worse. The duration of PD1 therapy was significantly associated with onset of pneumonitis (p=0.007).
Conclusion:
The site of primary tumor or metastasis may help predict the most common AEs in patients treated with PD1 inhibitors.
Insights
Characteristics of patients receiving programmed cell death-1 (PD1) inhibitors can predict adverse events (AEs). Primary tumor site influences AE risk, with specific cancers linked to higher odds of hypothyroidism, kidney injury, and pneumonitis.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacovigilance
Background:
- Limited data exists on patient characteristics associated with adverse events (AEs) from programmed cell death-1 (PD1) inhibitors.
- Understanding these characteristics is crucial for predicting and managing potential toxicities.
Purpose of the Study:
- To identify patient characteristics and primary tumor types associated with immune-related and non-immune-related adverse events (AEs) in patients treated with PD1 inhibitors.
- To inform risk stratification and personalized treatment strategies.
Main Methods:
- Retrospective analysis of 168 patients receiving single-agent PD1 inhibitors from August 2011 to August 2016.
- Adverse events were graded using Common Terminology Criteria for Adverse Events (CTCAE) v4.
Main Results:
- Patients with renal cell carcinoma (RCC) showed higher odds of grade 2+ kidney injury.
- Patients with Hodgkin's lymphoma and head and neck squamous cell carcinoma (HNSCC) had increased odds of grade 2+ hypothyroidism.
- Non-small cell lung cancer (NSCLC) patients experiencing pneumonitis had a higher risk of mortality.
Conclusions:
- Primary tumor site is a significant predictor of specific AEs in PD1 inhibitor therapy.
- RCC patients are susceptible to kidney injury, potentially due to prior nephrectomy.
- Pneumonitis in NSCLC patients treated with PD1 inhibitors is associated with worse survival and longer treatment duration.
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