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
3988 - Basal NK activity and early Treg function inhibition predicts Nivolumab responsiveness in metastatic renal cancer patients (REVOLUTION) trial.
Presenter: Sara Santagata
Session: Poster Display session 3
Resources:
Abstract
2142 - Low NK Cell Abundance Correlates with High Expression of PD-1 in CD8+ T Cells
Presenter: Moon Hee Lee
Session: Poster Display session 3
Resources:
Abstract
5501 - Tobacco smoking is associated with the immune suppressive microenvironment in head and neck squamous cell carcinoma (HNSCC)
Presenter: Christine Chung
Session: Poster Display session 3
Resources:
Abstract
5726 - Evaluation of Antibody-Dependent Cell Cytotoxicity (ADCC) in lung cancer cell lines treated with combined anti-EGFR and anti-PD-L1 therapy.
Presenter: Francesca Sparano
Session: Poster Display session 3
Resources:
Abstract
2534 - Radiomic Signatures for Identification of Tumors Sensitive to Nivolumab or Docetaxel in Squamous Non-Small Cell Lung Cancer (sqNSCLC)
Presenter: Laurent Dercle
Session: Poster Display session 3
Resources:
Abstract
3366 - Analysis of gut microbiota in advanced non-small cell lung cancer (NSCLC) patients treated with immune-checkpoints blockers
Presenter: FEIYU ZHANG
Session: Poster Display session 3
Resources:
Abstract
2089 - Pathogenesis of Myocarditis Following Treatment with Immune Checkpoint Inhibitors in a Cynomolgus Monkey Model
Presenter: Changhua Ji
Session: Poster Display session 3
Resources:
Abstract
4463 - Effects of dietary restriction in cancer patients receiving irinotecan
Presenter: Ruben Van Eerden
Session: Poster Display session 3
Resources:
Abstract
4841 - Investigating the Link between Burn Injury and Tumorigenesis
Presenter: Lucy Barrett
Session: Poster Display session 3
Resources:
Abstract
4619 - Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio in male breast cancer patients
Presenter: Joanna Huszno
Session: Poster Display session 3
Resources:
Abstract