Cancer Site and Adverse Events Induced by Immune Checkpoint Inhibitors: A Retrospective Analysis of Real-life Experience at a Single Institution.

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.