Kevin H Hall1, Yuan Liu2, Chen Jiang2, R Donald Harvey3,4. 1. Department of Pharmaceutical Services, Emory University Hospitals and Winship Cancer Institute, Atlanta, Georgia. 2. Department of Biostatistics and Bioinformatics, Rollins School of Public Health of Emory University, Atlanta, Georgia. 3. Departments of Hematology and Medical Oncology and Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, Georgia. 4. Winship Cancer Institute of Emory University, Atlanta, Georgia.
Abstract
STUDY OBJECTIVES: Immune checkpoint inhibitors have produced durable responses across a variety of cancers. Although programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors activate T cells against tumor cells, they may also cause autoimmune-like toxicities termed immune-related adverse events (irAEs). Although much is known regarding irAEs that occur early during treatment, data on the long-term toxicity profile of these agents are more limited. Our primary objective was to evaluate the frequency of patients receiving anti-PD-1/PD-L1 therapy for at least 6 continuous months who experienced new or worsening irAEs requiring clinical interventions. Secondary objectives included assessment of other factors associated with clinically significant irAEs after at least 6 months of therapy. DESIGN: Retrospective chart review. SETTING: Large university-affiliated National Cancer Institute-designated comprehensive cancer center. PATIENTS: A total of 159 adults diagnosed with any malignancy who received a PD-1/PD-L1 inhibitor-nivolumab, pembrolizumab, or atezolizumab-as monotherapy or with concurrent cytotoxic agents, for at least 6 months, between January 1, 2014, and September 1, 2017. MEASUREMENTS AND MAIN RESULTS: We collected information on the incidence and timing of irAEs, along with patient demographics and other treatment outcomes. Thirty-eight patients (24%) experienced clinically significant, new, or worsening irAEs after 6 months of treatment with anti-PD-1/PD-L1 therapy. Hypothyroidism was the most common irAE experienced (20 patients [12.6%]), followed by pneumonitis (5 patients [3%]); 2 patients died due to pneumonitis. Four patients (2.5%) had a deepened disease response beyond 6 months of treatment. CONCLUSION: Our results revealed that a significant proportion of patients continue to experience irAEs with long-term use of PD-1/PD-L1 inhibitors. These results further contribute to the risk-benefit understanding of chronic PD-1/PD-L1 antagonism and support discontinuation of these agents following deepest response.
STUDY OBJECTIVES: Immune checkpoint inhibitors have produced durable responses across a variety of cancers. Although programmed cell death protein 1 (PD-1) and its ligand (PD-L1) inhibitors activate T cells against tumor cells, they may also cause autoimmune-like toxicities termed immune-related adverse events (irAEs). Although much is known regarding irAEs that occur early during treatment, data on the long-term toxicity profile of these agents are more limited. Our primary objective was to evaluate the frequency of patients receiving anti-PD-1/PD-L1 therapy for at least 6 continuous months who experienced new or worsening irAEs requiring clinical interventions. Secondary objectives included assessment of other factors associated with clinically significant irAEs after at least 6 months of therapy. DESIGN: Retrospective chart review. SETTING: Large university-affiliated National Cancer Institute-designated comprehensive cancer center. PATIENTS: A total of 159 adults diagnosed with any malignancy who received a PD-1/PD-L1 inhibitor-nivolumab, pembrolizumab, or atezolizumab-as monotherapy or with concurrent cytotoxic agents, for at least 6 months, between January 1, 2014, and September 1, 2017. MEASUREMENTS AND MAIN RESULTS: We collected information on the incidence and timing of irAEs, along with patient demographics and other treatment outcomes. Thirty-eight patients (24%) experienced clinically significant, new, or worsening irAEs after 6 months of treatment with anti-PD-1/PD-L1 therapy. Hypothyroidism was the most common irAE experienced (20 patients [12.6%]), followed by pneumonitis (5 patients [3%]); 2 patients died due to pneumonitis. Four patients (2.5%) had a deepened disease response beyond 6 months of treatment. CONCLUSION: Our results revealed that a significant proportion of patients continue to experience irAEs with long-term use of PD-1/PD-L1 inhibitors. These results further contribute to the risk-benefit understanding of chronic PD-1/PD-L1 antagonism and support discontinuation of these agents following deepest response.
Authors: R Donald Harvey; Kathryn F Mileham; Vishal Bhatnagar; Jamie R Brewer; Atiqur Rahman; Cassadie Moravek; Andrew S Kennedy; Elizabeth A Ness; E Claire Dees; S Percy Ivy; Scot W Ebbinghaus; Caroline Schenkel; Thomas S Uldrick Journal: Clin Cancer Res Date: 2021-02-09 Impact factor: 13.801
Authors: Chunting Ye; Hongyuan Yang; Mingshan Cheng; Leonard D Shultz; Dale L Greiner; Michael A Brehm; James G Keck Journal: FASEB J Date: 2020-08-09 Impact factor: 5.834