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Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC).

Publication ,  Conference
Labriola, M; Zhu, J; Gupta, R; McCall, S; Jackson, J; White, JR; Weingartner, E; Kong, E; Simone, P; Papp, E; Gerding, K; Simmons, J ...
Published in: Journal of Clinical Oncology
May 20, 2019

e16079 Background: ICIs have revolutionized treatment for mRCC; however there are limited predictive biomarkers for response to ICIs. PD-L1 status is still controversial, demonstrating little predictive utility in mRCC. TMB is predictive for response to ICIs in melanoma and non-small cell lung cancer (NSCLC), but has not been validated in mRCC. Here, we assess the correlations between TMB and PD-L1 status with outcomes to ICI treatment in mRCC. Methods: 34 patients (pts) with mRCC who had previously received ICIs at Duke Cancer Institute were identified. Tumor samples were retrospectively evaluated using a Personal Genome Diagnostics Assay for somatic variants across > 500 genes, as well as TMB and microsatellite status. PD-L1 status was tested via the Dako 28-8 PD-L1 IHC assay. Deidentified clinical information was extracted from the medical record and tumor response was evaluated based on RECIST criteria. Results: Pts were grouped by overall response following ICI therapy into either progressive disease (“PD”, n = 18) or disease control group (“DC”, n = 16), defined as either stable disease, partial response, or complete response. Pts displayed a TMB range from 0.36 to 12.24 mutations/Mb with a mean score of 2.83 muts/Mb, with no significant difference between the PD and DC groups (mean 3.01 muts/Mb vs. 2.63 muts/Mb, p > 0.05). 9 of 32 evaluable samples were PD-L1 positive, with 4 in the PD group and 5 in the DC group. Notably, the DC group displayed a significant enrichment of mutations in genes affiliated with DNA repair (including BRCA1, BRCA2, FANCA, FANCB, FANCG, FANCM, MSH3, MSH6, RAD50, RAD51C, RAD51D, RAD54B, RECQL4, and SLX4; p = 0.0444). DNA damage gene mutations were found in 8/10 (80%) metastatic tumor specimens and 14/24 (58%) primary tumors. Conclusions: Overall, in this mRCC cohort, neither TMB nor PD-L1 correlated with patient outcomes or with ICI response. Furthermore, high TMB was not significantly associated with PD-L1 expression within the samples. The higher frequency of mutations in DNA repair genes in the DC group suggests potential use as a predictive signature for ICI response, warranting future prospective studies. Further studies with matched primary-metastatic samples would be beneficial to determine if DNA repair mutations occur more frequently in metastatic versus primary tumor specimens.

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

e16079 / e16079

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
Labriola, M., Zhu, J., Gupta, R., McCall, S., Jackson, J., White, J. R., … Zhang, T. (2019). Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC). In Journal of Clinical Oncology (Vol. 37, pp. e16079–e16079). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2019.37.15_suppl.e16079
Labriola, Matthew, Jason Zhu, Rajan Gupta, Shannon McCall, Jennifer Jackson, James R. White, Elizabeth Weingartner, et al. “Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC).” In Journal of Clinical Oncology, 37:e16079–e16079. American Society of Clinical Oncology (ASCO), 2019. https://doi.org/10.1200/jco.2019.37.15_suppl.e16079.
Labriola M, Zhu J, Gupta R, McCall S, Jackson J, White JR, et al. Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. e16079–e16079.
Labriola, Matthew, et al. “Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC).Journal of Clinical Oncology, vol. 37, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. e16079–e16079. Crossref, doi:10.1200/jco.2019.37.15_suppl.e16079.
Labriola M, Zhu J, Gupta R, McCall S, Jackson J, White JR, Weingartner E, Kong E, Simone P, Papp E, Gerding K, Simmons J, George DJ, Zhang T. Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2019. p. e16079–e16079.

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

e16079 / e16079

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

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