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
3073 - 1 patient 3 different advance Ca nurse’s roles: symptom management&continuum care through a joint approach in a clinical case
Presenter: Catarina Almeida
Session: Poster Display session 3
Resources:
Abstract
4527 - Identification of malnutrition risk factors in patients with cancer in the first nursing visit
Presenter: Amaia Valverde
Session: Poster Display session 3
Resources:
Abstract
2904 - Engaging Cancer Survivors, Healthcare Providers and Advocates in The Development of a Colorectal Cancer Survivorship Information Resource: A Participatory Action Research Study
Presenter: Amanda Drury
Session: Poster Display session 3
Resources:
Abstract
3435 - Medical nurses’ experiences of the care-needs of adult patients with a primary brain tumour
Presenter: Jamila Mohammed
Session: Poster Display session 3
Resources:
Abstract
857 - Feasibility and acceptability of a mHealth intervention to increase colonoscopy uptake among Chinese first-degree relatives: a pilot cluster randomized controlled trial
Presenter: Yang Bai
Session: Poster Display session 3
Resources:
Abstract
1087 - Cancer patient participation and compliance in microbiome sample collection: an oncology research nurse’s experience
Presenter: Julie Malo
Session: Poster Display session 3
Resources:
Abstract
2783 - Implementing Digital Individual Care plans for Patients with Head and Neck cancer- Challenges and opportunities
Presenter: Helena Ullgren
Session: Poster Display session 3
Resources:
Abstract
1152 - The Effect of the Short-term and Long-term Compassion Fatigue Resiliency Program on the Quality of Life, Perceived Stress and Psychological Resilience of Oncology-Hematology Nurses
Presenter: Tugba Pehlivan
Session: Poster Display session 3
Resources:
Abstract
1172 - Competing risk analyses of overall survival and cancer-specific survival in patients with orbital rhabdomyosarcoma after surgery: a large cohort study
Presenter: Yu Zhang
Session: Poster Display session 3
Resources:
Abstract
5949 - Communication of genetic information to family members in hereditary cancers and healthcare providers’ role
Presenter: Carla Pedrazzani
Session: Poster Display session 3
Resources:
Abstract