Abstract 4191
Background
Tumor-specific indicators, such as tumor mutation burden (TMB) have been shown to affect overall survival (OS) in melanoma. Recently, pan-cancer analyses from The Cancer Genome Atlas (TCGA) discovered specific tumor immune signatures predictive of overall survival (OS), yet it is unclear how these interact with other prognostic markers, independently of immunotherapy (IT). We aimed to combine the immune landscape signatures with TMB and other prognostic markers to improve melanoma OS prediction in patients, independent of IT.
Methods
We examined the whole-exome data in conjunction with the molecular, clinical and immune features from 278 metastatic melanomas from TCGA, not treated by IT, to develop an improved prognostic model of melanoma OS. Using the discovery (N = 139) and validation (N = 139) design we performed multivariate Cox proportional hazards (Cox HR) models, adjusted for age and tumor stage at primary diagnosis, to identify interaction between TMB and melanoma immune features (n = 59), refining the prediction of melanoma OS.
Results
We identified 4 immune features that were significantly associated with OS in both the discovery and validation cohorts. The multivariate Cox HR models revealed that IFN-γ response (IFN-γ R) and macrophage regulation (MR) signatures in combination with TMB were the most significantly associated with OS (p = 8.80E-14). After further refinement, we observed that patients with high TMB, high IFN-γ R and high MR had significantly better OS compared to high TMB, low IFN-y R and low MR (HR = 2.8, p = 3.55E-08). This association was not observed in low TMB patients.
Conclusions
We show, for the first time, that TMB and tumor immune features are significantly associated with improved OS, independent of IT. Further analysis of patients revealed that high TMB associates with improved OS in patients with high IFN- γ R and MR but not in low IFN- γ R and MR. Hence, this data provides first evidence that patients with high TMB have distinct OS outcome depending on other tumor immune features. Beside biological link between TMB and IFN-y and MR, our data suggest that these associations may significantly improve the current melanoma prognostic models.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J.S. Weber: Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Licensing / Royalties, Biomarker Patient: Biodesix. 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