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Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors
Julia Judd1, Matthew Zibelman2, Elizabeth Handorf3
1Department of Internal Medicine, Temple University Hospital, Philadelphia, Pennsylvania, USA.
Background:
The programmed death 1 (PD-1) checkpoint inhibitors (CKIs) can lead to immune-related adverse events (irAEs). We sought to evaluate whether the development of irAEs correlates with treatment response in non-melanoma malignancies.
Materials And Methods:
We conducted a retrospective study of patients who received anti-PD-1 CKI monotherapy at Fox Chase Cancer Center. Endpoints included overall response rate (ORR), time to next therapy or death (TTNTD), and overall survival (OS). Fisher's exact tests and logistic regression models were used to determine the association between irAE incidence and ORR, and Kaplan-Meier curves with log-rank tests and Cox regression models were used for the comparison of TTNTD and OS.
Results:
Between November 2011 and November 2016, 160 patients were treated with >1 dose of an anti-PD-1 CKI. Seventy-three (46%) were treated on a clinical trial. Immune-related adverse events were noted in 64 patients (40%), with steroids required in 36 (23%). Of the 142 patients evaluable for clinical response, 28 patients (20%) achieved a partial response at first scan. An association between irAEs and ORR was seen in clinical trial patients (p = .007), but not in non-trial patients (p = .13). When controlling for clinical trial participation and cancer type using multivariate analysis, low-grade irAEs had higher ORR (p = .017) and longer TTNTD (p = .008). No association between irAE incidence and OS was seen (p = .827). Immune-related adverse events that required steroid treatment were marginally associated with increased TTNTD (p = .05, hazard ratio 0.62) but were not associated with OS (p = .13).
Conclusion:
We demonstrate several positive associations between the development of irAEs and clinical outcomes in non-melanoma patients treated with PD-1 CKIs, for which further validation is required.
Implications For Practice:
This study evaluated whether the development of immune-related adverse events in non-melanoma patients treated with programmed cell death 1 checkpoint inhibitors correlates with improved clinical outcomes. The results indicate that for a subset of patients, in particular those with low-grade immune-related adverse events, immune-related adverse events predicted for an improved response rate and longer time to next therapy or death.
Insights
Immune-related adverse events (irAEs) from programmed death 1 (PD-1) checkpoint inhibitors correlate with better treatment response and longer time to next therapy or death in non-melanoma patients. Further validation is needed for these findings.
Area of Science:
- Oncology
- Immunology
- Clinical Research
Background:
- Programmed death 1 (PD-1) checkpoint inhibitors (CKIs) are utilized in treating various cancers.
- Immune-related adverse events (irAEs) are known side effects of PD-1 CKIs.
- The correlation between irAEs and treatment efficacy in non-melanoma malignancies requires further investigation.
Purpose of the Study:
- To evaluate the association between the development of irAEs and treatment response in patients with non-melanoma malignancies receiving PD-1 CKI monotherapy.
- To determine if irAEs correlate with overall response rate (ORR), time to next therapy or death (TTNTD), and overall survival (OS).
Main Methods:
- Retrospective study of 160 patients treated with anti-PD-1 CKI monotherapy.
- Analysis of ORR, TTNTD, and OS as endpoints.
- Statistical methods included Fisher's exact tests, logistic regression, Kaplan-Meier curves, log-rank tests, and Cox regression models.
Main Results:
- 40% of patients experienced irAEs; 23% required steroids.
- Low-grade irAEs were associated with higher ORR (p=0.017) and longer TTNTD (p=0.008) in multivariate analysis.
- No significant association was observed between irAEs and overall survival (OS).
Conclusions:
- The development of irAEs is associated with improved clinical outcomes, including response rates and time to next therapy or death, in non-melanoma patients treated with PD-1 CKIs.
- Low-grade irAEs appear to be a positive predictive biomarker for treatment response.
- Further research is warranted to validate these associations.
