In a retrospective cohort study reported in JAMA Oncology, Shankar et al found improved progression-free and overall survival among patients who experienced multisystem immune-related adverse events after anti–PD-1 or anti–PD-L1 immune checkpoint inhibitor therapy for stage III/IV non–small cell lung cancer (NSCLC).
Study Details
The study involved 623 patients from five centers worldwide who received anti–PD-1/PD-L1 immune checkpoint inhibitors alone or in combination with another anticancer agent between January 2007 and January 2019.
Multisystem immune-related adverse events were characterized by combinations of individual immune-related adverse events or organ system involved.
Key Findings
Among the 623 patients (60% male, 77% white, median age = 66 years), 527 received anti–PD-1/PD-L1 monotherapy and 96 received combination treatments. Overall, 148 patients (24%) developed a single immune-related adverse event, and 58 (9.3%) developed multisystem immune-related adverse events. All multisystem immune-related adverse events occurred sequentially.
Among patients receiving anti–PD-1/PD-L1 monotherapy, 135 developed a single immune-related adverse event and 51 developed multisystem immune-related adverse events. Among those who experienced multisystem immune-related adverse events, the most common patterns were pneumonitis-thyroiditis (n = 7, 14%), hepatitis-thyroiditis (n = 5, 10%), dermatitis-pneumonitis (n = 5, 10%), and dermatitis-thyroiditis (n = 4, 8%).
Among patients receiving combination treatment, 13 developed single and 7 developed multisystem immune-related adverse events. No patterns of multisystem immune-related adverse events were observed among patients receiving combination treatment.
KEY POINTS
- Median progression-free survival for the multisystem vs single vs no immune-related adverse event groups was 10.9 months vs 5.1 months vs 2.8 months, with 1-year rates of 44%, 28%, and 16%.
- Median overall survival for multisystem vs single vs no immune-related adverse event groups was 21.8 months vs 12.3 months vs 8.7 months.
Factors independently associated with development of multisystem immune-related adverse events were Eastern Cooperative Oncology Group performance status of 0/1 vs 2 (adjusted odds ratio [OR] = 0.27, P = .04) and longer immune checkpoint inhibitor therapy duration (adjusted OR = 1.02, P < .001).
Median progression-free survival for the multisystem vs single vs no immune-related adverse event groups was 10.9 months vs 5.1 months vs 2.8 months (P < .001), with 1-year rates of 44%, 28%, and 16%. In multivariate analysis adjusting for checkpoint inhibitor duration, adjusted hazard ratios vs no immune-related adverse events were 0.68 (P < .001) for 1 event and 0.39 (P < .001) for multisystem events.
Median overall survival for multisystem vs single vs no immune-related adverse event groups was 21.8 months vs 12.3 months vs 8.7 months. In multivariate analysis adjusting for checkpoint inhibitor duration, adjusted hazard ratios vs no immune-related adverse events were 0.86 (P = .26) for single events and 0.57 (P = .005) for multisystem events.
Overall, there was a significant positive association between immune-related adverse event number and progression-free survival (HR = 0.67, P < .001) and overall survival (HR = 0.79, P = .003).
The investigators concluded, “In this multicenter cohort study, development of multisystem immune-related adverse events was associated with improved survival in patients with advanced NSCLC treated with immune checkpoint inhibitors.”
Jarushka Naidoo, MBBCH, MHS, of The Royal College of Surgeons of Ireland, Beaumont Hospital, Dublin, is the corresponding author for the JAMA Oncology article.
Disclosure: This study was funded by the Bloomberg~Kimmel Institute for Cancer Immunotherapy, National Institutes of Health, and The Ohio State University Center for Clinical and Translational Science. For full disclosures of the study authors, visit jamanetwork.com.
