Abstract 5884
Background
The era of immunotherapy changed considerably prognosis of melanoma. Nonetheless, only around 40% can get benefit from this treatment, with no biomarkers identified for the therapeutic choice. On the basis of emerging clinical evidence, increased Tumor Mutational Burden (TMB) may be associated with higher sensitivity to immunotherapeutic agents.
Methods
The aim of this study was to analyze in advanced melanoma the relationship between the mutation load and: i) the histologic characteristics, ii) locations according to sun exposure and iii) response to PD-1 inhibitors, in advanced melanoma patients, in a retrospective multicentric analysis by sequencing using FoundationOne®. TMB was characterized as the number of somatic protein-coding base substitution or alterations mutations per megabase (Mb). DNA was extracted from paraffin embedded sections of primary tumor or metastasis. TMB was considered low between 1 and 5 muts/Mb, intermediate between 6 and 19, high if > 20 muts/Mb.
Results
In five centers in France, we included between October 2017 and March 2019 101 patients, aged from 16-year to 92-year-old, with metastatic melanomas. Results were available for 89 cases (12% DNA extraction failure). Acral (n = 6, 20%), mucosal (n = 5, 17%) and uveal melanoma (n = 4, 13%) had a lower TMB compared to sun-exposed melanomas. No melanoma of non-sun-exposed areas had high burden (n = 0); intermediate TMB was found in 21% (n = 8) and low TMB in 63% of cases (n = 19). Conversely, melanoma on chronic exposed areas (face and neck) had high TMB (5/7 cases; 71%). Complete and partial remission after 3 months of anti-PD-1 were more often observed in TMB high patients (n = 4;20%) whereas in low and intermediate mutational patients, progression was found in respectively 62% (n = 24) and 53% (n = 16).
Conclusions
TMB is affected by a variety of causes, including ultraviolet light in melanoma and smoking in lung cancer. Desmoplastic melanomas have been reported to have a high prevalence of somatic mutations whereas mucosal and acral have a 5-to 10-fold lower. Our study highlights the importance of TMB with higher response to PD-1 blockade. While it has to be confirmed, sun exposed areas or UV-signature may in be a valuable criterion in helping clinical decision-making.
Clinical trial identification
Editorial acknowledgement
Foundation One Medicine and Roche Laboratories.
Legal entity responsible for the study
French hospitals.
Funding
Has not received any funding.
Disclosure
C. Allayous: Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen. All other authors have declared no conflicts of interest.
Resources from the same session
1715 - National Small Cell Bladder Cancer Audit: Results from 26 UK institutions
Presenter: Caroline Chau
Session: Poster Display session 3
Resources:
Abstract
2108 - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase 3 study.
Presenter: Michiel Van der Heijden
Session: Poster Display session 3
Resources:
Abstract
3090 - Comparison of Immuno-Oncology (IO) Biomarkers in Adenocarcinoma (ACB), Urothelial Carcinoma (UCB) and Squamous Cell Carcinoma (SCCB) of the Bladder, with interim results from PURE01
Presenter: Daniele Raggi
Session: Poster Display session 3
Resources:
Abstract
5211 - Potential role of a clinical, taxonomical classification and RNA expression integrated signature to predict response to neoadjuvant platinum-based chemotherapy in muscle-invasive bladder cancer (MIBC) patients
Presenter: Albert Font
Session: Poster Display session 3
Resources:
Abstract
3206 - Hyperphosphatemia due to Erdafitinib (a Pan-FGFR Inhibitor) and Anti-tumor Activity Among Patients (Pts) with Advanced Urothelial Carcinoma (UC)
Presenter: Scott Tagawa
Session: Poster Display session 3
Resources:
Abstract
3110 - Prognostic role of FGFR Mutations and FGFR mRNA expression in metastatic urothelial cancer treated with anti-PD(L1) inhibitors in first and second line setting
Presenter: Florian Roghmann
Session: Poster Display session 3
Resources:
Abstract
3564 - Circulating tumour DNA (ctDNA) utility as a biomarker for metastatic urothelial carcinoma (mUC)
Presenter: Jean-Michel Lavoie
Session: Poster Display session 3
Resources:
Abstract
2760 - Comparative analysis of tumor mutational burden (TMB) prediction methods and its association with determinants of the tumor immune microenvironment of urothelial bladder cancer (UBC)
Presenter: Markus Eckstein
Session: Poster Display session 3
Resources:
Abstract
2513 - The Immunoscore in patients with urothelial carcinoma treated with neoadjuvant chemotherapy: clinical significance for pathological response and survival
Presenter: Elise Nassif
Session: Poster Display session 3
Resources:
Abstract
2835 - Genomic analysis of urothelial cancer and associations with treatment choice and outcome
Presenter: David Sarid
Session: Poster Display session 3
Resources:
Abstract