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
4596 - A Phase 2, Open-Label, Randomized, Multicenter Trial of Encorafenib + Binimetinib Evaluating a Standard-dose and a High-dose Regimen in Patients With BRAFV600-Mutant Melanoma Brain Metastasis (MBM) (POLARIS)
Presenter: Michael Davies
Session: Poster Display session 3
Resources:
Abstract
1891 - Continuation of annual screening mammograms and breast-cancer mortality in women over 70
Presenter: Xabier Garcia De Albeniz
Session: Poster Display session 3
Resources:
Abstract
5587 - Introducing standardized medical procedure and dynamic decision support program in precision oncology for the community of practice
Presenter: Istvan Petak
Session: Poster Display session 3
Resources:
Abstract
4757 - Effectively using primary care givers in oncology care through capacity building, task sharing and techno-mentoring.
Presenter: Dinesh Pendharkar
Session: Poster Display session 3
Resources:
Abstract
4497 - A single institution review of capecitabine related acute admissions and cost analysis
Presenter: Gemma Dart
Session: Poster Display session 3
Resources:
Abstract
2187 - Health status of middle-aged and older cancer survivors in China: results from the China Health and Retirement Longitudinal Study (CHARLS)
Presenter: Jiarui Li
Session: Poster Display session 3
Resources:
Abstract
5101 - Crossed looks on lung cancer perception and knowledge from general public and physicians in France: results of a two-fold survey
Presenter: Céline Mascaux
Session: Poster Display session 3
Resources:
Abstract
4354 - Knowledge and perception of clinical trials (CTs) and attitude towards participation among Polish oncological patients - A pilot survey
Presenter: Artur Kotowski
Session: Poster Display session 3
Resources:
Abstract
3499 - Achieving best possible cancer treatment outcomes in care pathways through benchmarking; ABC-Benchmarking
Presenter: Anke Wind
Session: Poster Display session 3
Resources:
Abstract
2270 - Impact of 10-day Fulbright Specialist Program (FSP) and Project Pink Blue (PPB) Education Sessions on Medical Oncology knowledge among Doctors that treat cancer in Nigeria
Presenter: Mike Martin
Session: Poster Display session 3
Resources:
Abstract