Immune-related adverse events as a biomarker in non-melanoma patients treated with programmed cell death 1 inhibitors

Julia Judd, Matthew Zibelman, Elizabeth Handorf, John O’Neill, Chethan Ramamurthy, Sasini Bentota, Jamie Doyle, Robert G. Uzzo, Jessica Bauman, Hossein Borghaei, Elizabeth R. Plimack, Ranee Mehra, Daniel M. Geynisman

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

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. Immunerelated 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 (p5.007), but not in non-trial patients (p5.13). When controlling for clinical trial participation and cancer type using multivariate analysis, low-grade irAEs had higher ORR (p5.017) and longer TTNTD (p5.008). No association between irAE incidence and OS was seen (p5.827). Immune-related adverse events that required steroid treatment were marginally associated with increased TTNTD (p5.05, hazard ratio 0.62) but were not associated with OS (p5.13). 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.

Original languageEnglish (US)
Pages (from-to)1232-1237
Number of pages6
JournalOncologist
Volume22
Issue number10
DOIs
StatePublished - Oct 2017
Externally publishedYes

Keywords

  • Checkpoint inhibitors
  • Immune-related adverse events
  • Immunotherapy
  • Nivolumab
  • Pembrolizumab
  • Programmed cell death 1 inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Judd, J., Zibelman, M., Handorf, E., O’Neill, J., Ramamurthy, C., Bentota, S., Doyle, J., Uzzo, R. G., Bauman, J., Borghaei, H., Plimack, E. R., Mehra, R., & Geynisman, D. M. (2017). Immune-related adverse events as a biomarker in non-melanoma patients treated with programmed cell death 1 inhibitors. Oncologist, 22(10), 1232-1237. https://doi.org/10.1634/theoncologist.2017-0133