Skip to main content

Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC).

Publication ,  Conference
Zhu, J; Pabla, S; Labriola, M; Gupta, RT; McCall, S; George, DJ; Dressman, D; Glenn, S; George, S; Morrison, C; Zhang, T
Published in: Journal of Clinical Oncology
May 20, 2019

2595 Background: ICIs are now standard of care for mRCC; however, there are few biomarkers to predict ICI response. Recent data from atezolizumab/bevacizumab trials in mRCC suggest tumors with high T/PD-L1+ are more likely to respond to ICI. Here, we use two gene panels as well as other inflammation markers in the tumor microenvironment to correlate with ICI responses. Methods: This multicenter study evaluated 86 patients (pts) with mRCC treated with ICIs. FFPE tumor samples were evaluated by RNA sequencing for T status. Two gene panels were analyzed: a T Gene Panel (CD8, CD27, IFNG, GZMA, GZMB, PRF1, EOMES, CXCL9, CXCL10, CXCL11, CD274, CTLA4, FOXP3, TIGIT, IDO1, PSMB9, TAP1) and a 5-Gene panel (FOXP3, CCR4, KLRK1, ITK, and TIGIT) based on the gene expression pattern of tumors in our cohort. Objective response rates (ORRs, defined as CRs and PRs) were correlated with PD-L1 status (positivity was defined as ≥1% TPS based on Dako 22C3 IHC assay), and TMB (0-10, 10-20, ≥20 mut/Mb), and tumor inflammation (high CD8 expression compared to a large reference population). Best responses to ICI was determined by an expert radiologist using RECIST 1.1 criteria. Inflamed tumor status, T gene panel, 5-gene panel, PD-L1 status, and TMB were associated with ORR and tested using a chi-squared test with Yates’s continuity correction. Results: ORR was 50% (4/8) for PD-L1 positive pts and 14% (9/65) for PD-L1 negative pts (p = 0.042). The majority of tumors (95%, 82/86) had TMB < 10 mut/mb. 43 pts (50%) were classified as T and 43 pts were classified as T. ORR was 23% (10/43) in the T cohort and 12% (5/43) in the T cohort (p = 0.256). ORR was 31% (14/45) in the 5-Gene high cohort and 2% (1/41) in the 5-Gene low cohort (p = 0.001). Conclusions: TMB and tumor inflammation based on CD8 did not reliably predict for objective responses in this study of mRCC pts treated with ICIs. Gene expression signatures provide a more comprehensive evaluation of the tumor microenvironment and may lead to better predictive biomarkers for ICI response than individual biomarkers such as PD-L1, TMB, or CD8 expression.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2019

Volume

37

Issue

15_suppl

Start / End Page

2595 / 2595

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhu, J., Pabla, S., Labriola, M., Gupta, R. T., McCall, S., George, D. J., … Zhang, T. (2019). Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC). In Journal of Clinical Oncology (Vol. 37, pp. 2595–2595). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2019.37.15_suppl.2595
Zhu, Jason, Sarabjot Pabla, Matthew Labriola, Rajan T. Gupta, Shannon McCall, Daniel J. George, Devin Dressman, et al. “Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC).” In Journal of Clinical Oncology, 37:2595–2595. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.15_suppl.2595.
Zhu J, Pabla S, Labriola M, Gupta RT, McCall S, George DJ, et al. Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. 2595–2595.
Zhu, Jason, et al. “Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC).Journal of Clinical Oncology, vol. 37, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 2595–2595. Crossref, doi:10.1200/jco.2019.37.15_suppl.2595.
Zhu J, Pabla S, Labriola M, Gupta RT, McCall S, George DJ, Dressman D, Glenn S, George S, Morrison C, Zhang T. Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. 2595–2595.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2019

Volume

37

Issue

15_suppl

Start / End Page

2595 / 2595

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences