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
5383 - A pilot trial to investigate the impact of a personalised self-management lifestyle programme using mobile technology on the health and wellbeing of cancer survivors
Presenter: Mary Grace Kelly
Session: Poster Display session 3
Resources:
Abstract
5084 - The BRIGHTLIGHT national survey of the impact of specialist teenage and young adult cancer care on caregivers’ information and support needs
Presenter: Rachel Taylor
Session: Poster Display session 3
Resources:
Abstract
4328 - Life beyond cancer: Occupational health care service support in returning work experienced by cancer survivals
Presenter: Minna Nurmi
Session: Poster Display session 3
Resources:
Abstract
3337 - Investigating the factors related to primary caregivers' burden in oncology patients in Greece
Presenter: Ourania Govina
Session: Poster Display session 3
Resources:
Abstract
3387 - Factors Influencing the Level of Emotional Support from Nurses Perceived by Patients Undergoing Haematopoietic Stem Cell Transplantation in Protective Isolation
Presenter: Michela Piredda
Session: Poster Display session 3
Resources:
Abstract
935 - Progressive Muscle Relaxation and Guided Imagery Techniques and the Way of Coping of Parents of Children with Malignancies: A randomized controlled trial
Presenter: Tsitsi Theologia
Session: Poster Display session 3
Resources:
Abstract
3457 - Pharmacist and Nurse Led Melanoma Immunotherapy Clinic
Presenter: Dharmisha Chauhan
Session: Poster Display session 3
Resources:
Abstract
5160 - Measuring the impact of the Irish Cancer Society's Cancer Information Services
Presenter: Aileen McHale
Session: Poster Display session 3
Resources:
Abstract
4297 - It's Great to Talk
Presenter: Noreen Andersen
Session: Poster Display session 3
Resources:
Abstract
4444 - Impact of Burn-Out Syndrome in Oncology personnel and its improvement through specific interventions
Presenter: Inmaculada Ortega
Session: Poster Display session 3
Resources:
Abstract