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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, ST; Nesline, M; George, S; Morrison, C; Zhang, T
Published in: Journal of Clinical Oncology
March 10, 2019

63 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 this T gene panel as well as other markers of inflammation in the tumor microenvironment to correlate with ICI responses. Methods: This multicenter study evaluated 69 pts with mRCC treated with ICIs. FFPE tumor samples were evaluated by RNA sequencing to measure transcript levels of genes related T status. T status was defined as the mRNA expression of 17 genes (CD8, CD27, IFNG, GZMA, GZMB, PRF1, EOMES, CXCL9, CXCL10, CXCL11, CD274, CTLA4, FOXP3, TIGIT, IDO1, PSMB9, TAP1), with T separated at the median. PD-L1 positivity was defined as ≥1% TPS based on Dako 22C3 IHC assay, and TMB high as > 10 mutations per megabase. Inflamed tumors were defined as CD8 expression in the top 75th percentile compared to a large reference population of multiple tumor types. Best responses to ICI was determined by an expert radiologist using RECIST 1.1 criteria. Inflamed tumor status, T gene expression, PD-L1 positive, and TMB were associated with disease control (DC, defined as CR, PR, or stable disease). DC comparisons were tested using a chi-squared test with Yates’s continuity correction. Results: DC was 63% (5/8) amongst PD-L1 positive pts and 52% (31/60) in PD-L1 negative patients (p = 0.84). Only 2 pts were TMB high. The majority of mRCC tumors (97%, 67/69) were TMB low. 6-month DC in TMB high tumors was 50% (1/2) and 49.3% (33/67) in TMB low tumors (p = 1.0). 36 pts were classified as T and 33 patients were classified as T. 6-month DC was 61% (22/36) in the T cohort and 36% (12/33) in the T cohort (p = 0.069). 6-month DC was 64% of inflamed tumors (16/25) vs 41% of non-inflamed tumors (18/44) (p = 0.111). Conclusions: TMB high and PD-L1 expression do not reliably predict for DC in pts with mRCC. Utilizing a gene signature score may better predict ICI response.

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Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

March 10, 2019

Volume

37

Issue

8_suppl

Start / End Page

63 / 63

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. 63–63). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2019.37.8_suppl.63
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, 37:63–63. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.8_suppl.63.
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. 63–63.
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. 8_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 63–63. Crossref, doi:10.1200/jco.2019.37.8_suppl.63.
Zhu J, Pabla S, Labriola M, Gupta RT, McCall S, George DJ, Dressman D, Glenn ST, Nesline M, 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. 63–63.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

March 10, 2019

Volume

37

Issue

8_suppl

Start / End Page

63 / 63

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

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