Abstract 2760
Background
TMB is an emerging biomarker for immune-therapy including metastasized UBC. The evaluation of reliable methods to determine the TMB value is a prerequisite for successful application of IO therapies.
Methods
TMB was assessed in genomic DNA from 39 muscle-invasive UBC by whole genome sequencing (GPS Cancer©, NantHealth). In 45 cases sequencing with the TruSight Oncology 500, (TSO500, Illumina) was performed. Immune cell (IC) infiltrates were analyzed by CD3, CD8, CD56, PD-1 and CD68 immunohistochemistry. PD-L1 status was evaluated by the SP263 assay (Ventana). Intrinsic subtypes (MDACC-approach) were assessed via a Nanostring-assay. Immune phenotypes were assessed by (I) spatial distribution of IC and (II) a T-cell inflammation related gene expression signature consisting of 29 genes (Nanostring). Results were validated in the TCGA MIBC cohort.
Results
Correlation between TSO500 and WGS revealed high concordance (spearman-correlation: r = 0.68, p < 0.0001). Overall percentage agreement was 76.9% for a cut-off of 10 mut/mb and 84.6% for 15 mut/mb. We found no significant association of high TMB at different cut-offs (10 mut/mb, 15 mut/mb) with inflammation status and different immune cell populations in both cohorts. TMB was not associated with intrinsic subtypes. Spatially distributed IC phenotypes or PD-L1 status was not associated with TMB. Hierarchical clustering of all factors revealed four distinct subgroups: Cluster A Inflamed, PD-L1 “high”, TMB high (n = 5); Cluster B Inflamed, PD-L1 “high”, TMB low-intermediate (n = 14); Cluster C: Uninflamed, PD-L1 “low”, TMB intermediate-high (n = 14); Cluster D Uninflamed, PD-L1 “low”, TMB low (n = 12).
Conclusions
This study provides insights into the reliability of a NGS panel for the prediction of TMB in MIBC which shows comparable performance to WGS. High TMB seems to be a characteristic of MIBC which occurs regardless of PD-L1 and inflammation status. TMB could possibly identify additional patients who do not fulfill the PD-L1 assessment based criteria for checkpoint inhibition.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Illumina, California, United States of America NantHealth, Culver City, California, United States of America.
Disclosure
M. Eckstein: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Janssen-Cilag. All other authors have declared no conflicts of interest.
Resources from the same session
2262 - Real world experience of Nivolumab therapy in Metastatic Renal Cancer patients: a 3 year multi-centre review
Presenter: Joanna Hack
Session: Poster Display session 3
Resources:
Abstract
4441 - “A pilot study of tremelimumab (treme) with or without cryoablation (cryo) in patients (pts) in metastatic renal cell carcinoma (mRCC).”
Presenter: Matthew Campbell
Session: Poster Display session 3
Resources:
Abstract
2613 - Lenvatinib (Len) alone or in combination with Everolimus (Eve) in heavily pretreated patients (pts) with metastatic renal cell carcinoma (mRCC) after immune checkpoint inhibitors (ICI) and VEGFR-targeted therapies: A single-institution experience
Presenter: Andrew Wiele
Session: Poster Display session 3
Resources:
Abstract
3249 - Weight loss is an underestimated adverse event with cabozantinib in patients with metastastic renal cell carcinoma (mRCC).
Presenter: Emeline Colomba
Session: Poster Display session 3
Resources:
Abstract
2405 - Impact of corticosteroids on nivolumab activity in metastatic clear cell renal cell carcinoma.
Presenter: Felix Lefort
Session: Poster Display session 3
Resources:
Abstract
4020 - Skeletal muscle loss as an adverse event during Cabozantinib treatment in patients with metastatic renal cell carcinoma
Presenter: Carolina Alves Costa Silva
Session: Poster Display session 3
Resources:
Abstract
2407 - Long term relative survival (RS) in patients with primary metastatic kidney cancer (primary mRCC): an analysis of 2,167 patients from the Austrian National Cancer Registry (ANCR).
Presenter: Monika Hackl
Session: Poster Display session 3
Resources:
Abstract
2470 - Advanced renal cell carcinoma: first results from the prospective research platform CARAT for patients with mRCC in Germany
Presenter: Peter Goebell
Session: Poster Display session 3
Resources:
Abstract
1533 - Are immune checkpoint inhibitors a valid option for papillary Renal Cell Carcinoma? Transcriptomic characterization of the immune infiltrate
Presenter: Manon De Vries-brilland
Session: Poster Display session 3
Resources:
Abstract
3367 - Treatment-Free Survival, With and Without Toxicity, as a Novel Outcome Applied to Immuno-Oncology Agents in Advanced Renal Cell Carcinoma
Presenter: Meredith Regan
Session: Poster Display session 3
Resources:
Abstract