Skip to main content


  • Poster presentation
  • Open Access

Markers of inflammation are associated with clinical outcomes in patients with metastatic renal cell carcinoma treated with nivolumab

  • 1,
  • 2,
  • 3,
  • 4,
  • 5,
  • 6,
  • 7,
  • 8,
  • 9,
  • 10,
  • 11,
  • 12,
  • 13,
  • 14,
  • 15,
  • 15,
  • 15,
  • 15,
  • 15 and
  • 16
Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P197

  • Published:


  • Overall Survival
  • Ipilimumab
  • Metastatic Renal Cell Carcinoma
  • Immune Checkpoint
  • Longe Overall Survival


In previously treated patients with metastatic renal cell carcinoma (mRCC), the programmed death-1 (PD-1) inhibitor antibody nivolumab demonstrated objective response rates of 20%–22% and median overall survival (OS) of 18.2– 25.5 months[1]. An exploratory biomarker analysis of baseline and on-therapy changes was conducted to investigate the relationship between the clinical and immunomodulatory activity of nivolumab.


Patients with 1–3 prior therapies for mRCC received nivolumab 0.3, 2, or 10 mg/kg IV every 3 weeks (Q3W); treatment-naïve patients received 10 mg/kg IV Q3W. Biopsies and peripheral blood mononuclear cells were obtained at baseline and cycle 2 day 8. Tumor burden reduction was defined as a ≥20% decrease. Gene expression data were obtained on Affymetrix U219. OS parameters were estimated by the Kaplan-Meier method or by Cox proportional hazards regression. PD-1 ligand 1 (PD-L1) expression was measured by tumor membrane immunohistochemical staining (28-8 antibody; Dako) in baseline biopsies. Serum-soluble factors were quantified using a Luminex multiplex panel (Myriad Rules-Based Medicine). T cell receptor sequencing was conducted with the immunoSEQ assay (Adaptive Biotechnologies).


91 patients were treated. 59 baseline and 55 on-therapy biopsies were evaluable for gene expression, with 42 matched samples. Patients with tumor burden reduction had differential expression (>1.3-fold, P < 0.01, q-value < 0.16) of 311 genes at baseline (n = 13) and 779 genes on-therapy (n = 11) compared with patients without tumor burden reduction, including higher expression of transcripts associated with cell-mediated immunity. CTLA-4, TIGIT, and PD-L2 transcripts were present at higher levels on-therapy in patients with tumor burden reduction. Table 1 summarizes OS and OS by PD-L1 expression. 18/56 biopsies (32%) had ≥5% PD-L1 expression. Among serum-soluble factors, recognized prognostic markers (VEGF, ICAM1, VCAM1, TIMP1) were associated with OS. Based on T cell sequencing, increased tumor T cell counts and decreased blood T cell clonality at baseline were associated with longer OS.

Table 1


Median OS, mo (95% CI)

OS rate, % (95% CI)




Treatment group


 0.3 mg/kg (n=22)

16.4 (10.1-NR)

71 (47-86)

44 (22-64)

 2.0 mg/kg (n=22)


72 (48-86)

61 (36-78)

 10 mg/kg (n=23)

25.2 (12.0-NR)

74 (48-88)

51 (27-71)

 10 mg/kg (naïve) (n=24)


81 (57-92)

76 (51-89)

PD-L1 expression


 ≥5% (n=18)


71 (44-87)

64 (37-82)

<5% mg/kg (n=38)

23.4 (13.1-33.3)

71 (52-83)

48 (30-64)

NR = not reached


Immune markers at baseline and on-therapy suggest pre-existing adaptive immunity is associated with nivolumab-induced tumor regression. Upregulation of immune checkpoint molecules provides rationale for study of nivolumab and ipilimumab combination in mRCC. A minimal difference in OS by PD-L1 expression was observed for up to 2 years.

Trial registration identifier NCT01358721.



Dako, for collaborative development of the automated PD-L1 immunohistochemistry assay. Adaptive Biotechnologies, for T cell repertoire analysis.

Authors’ Affiliations

Yale Comprehensive Cancer Center, New Haven, CT, USA
Department of Medical Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
The Cytokine Working Group; Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA
Department of Medical Oncology, Yale Cancer Center, New Haven, CT, USA
University of Chicago Medicine, Chicago, IL, USA
Department of Oncology, University Clinic of Navarra, Pamplona, Spain
Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA
Providence Cancer Center, Providence Portland Medical Center, Portland, OR, USA
Department of Surgery, Duke University Medical Center, Durham, NC, USA
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
Department of Medicine, University of Pittsburgh Medical Center Cancer Pavilion, Pittsburgh, PA, USA
Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA
Bristol-Myers Squibb, Princeton, NJ, USA
Department of Medicine, Dana-Farber Cancer Institute, Boston, MA, USA


  1. Motzer RM, et al: Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015, 33: 1430-1437.PubMedView ArticleGoogle Scholar


© Sznol et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.