3348 - Tumor mutational burden and immune infiltrates in primary renal cell carcinoma and matched brain metastases

Background

High tumor mutational burden (TMB) as well as high density of tumor infiltrating lymphocytes (TIL) have been postulated as predictive response biomarkers for immune checkpoint inhibitor-based therapies. Therefore, we aimed to investigate the concordance of TMB and TIL in a series of primary/extracranial renal cell carcinoma specimens and matched brain metastases (BM).

Methods

Specimens from 10 patients with brain metastatic renal cell carcinoma were retrieved from the Vienna Brain Metastasis Registry (6/10 primary renal cell tumor, 4/10 lung metastasis, 10/10 matched BM). TMB was assessed using the TruSight Oncology 500 gene panel with libraries sequenced on a NextSeq instrument. TIL subsets (CD3+, CD8+) were investigated using the Ventana Benchmark Ultra system for immunohistochemistry and automated tissue analysis (Definiens software).Spearman correlation coefficient (SCC) and paired t-test were used to correlate and compare scale variables.

Results

Median TMB was 5.4 mut/Mb (range 0-8.6 mut/Mb) in extracranial samples and 5.9 mut/Mb (range 3.1 – 59.6 mut/Mb) in BM (p > 0.05; paired t-test). Median density of CD3+ TIL in extracranial samples was 3.7/nm² (range 4.9 – 7.1/nm²) and 5.2/nm² (range 7.0 – 9.8/nm²) in BM (p > 0.05; paired t-test). Median density of CD8+ TIL was 3.2/nm² (range 4.4 – 8.7/nm²) in extracranial samples and 3.7/nm² (range 5.9 – 8.8/nm²) in BM (p > 0.05; paired t-test). No significant correlation of CD3+ TIL density and TMB (SCC: 0.02), CD8+ TIL density and TMB (SCC: 0.42) nor CD3+ and CD8+ TIL density (SCC: 0.18; p > 0.05) was observed in the present cohort.

Conclusions

TMB and TIL density were numerically higher in BM compared to the matched extracranial samples in the present cohort. Although results have to be interpreted with caution due to the limited sample size, our results support the further exploration of immune checkpoint inhibitors also in patients with BM from renal cell carcinoma.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Preusser: Research grant / Funding (self): Böhringer-Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck Sharp & Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Gerson Lehrman Group; Honoraria (self), Advisory / Consultancy: CMC Contrast; Honoraria (self), Advisory / Consultancy: Mundipharma; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medahead; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo. A.S. Berghoff: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Daiichi Sankyo; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Bristol-Meyers Squibb; Honoraria (self), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AbbVie. All other authors have declared no conflicts of interest.