Abstract 1133P
Background
Metastatic uveal melanoma (MUM) is a rare and lethal disease with varied clinical course. Despite the existence of well-characterized molecular drivers none have been associated with clinical outcomes in MUM. We aimed to study how uveal melanoma genetic alterations affect MUM prognosis.
Methods
From a prospective database of MUM patients, we analysed molecular alterations of primary tumors, including mutations (GNAQ/GNA11 and SF3B1) and chromosomal imbalances (chr3 monosomy (M3),chr8q amplification (+8q), chr8p deletion (-8p),chr8p amplification (+8p), chr1p deletion (-1p), chr6p deletion (-6p), and chr6q amplification (+6q)). Relevant clinical features at the time of MUM diagnosis, such as age, sex, disease-free survival from primary tumor, ECOG score, size of liver metastasis, and levels of LDH, alkaline phosphatase (ALP), bilirubin (BIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were recorded. Survival analysis was calculated from MUM diagnosis to death or last follow-up.
Results
Molecular data was obtained from 59 of 119 MUM patients treated at our institution from 2007 to 2022. The mutational driver profile was: 46% GNAQ and 40% GNA11; 42% Q209P and 44% Q209L; 19% SF3B1 mutation being 10% R625H, and 9% R625C. Chromosomal alterations were: M3 81%, +8q 60%, +8p 15%, -8p 12%, -1p 30%, -6q 17%, and +6p 17%. The median overall survival (mOS) for the entire cohort was 16 months(m). Among all genetic alterations, only SF3B1 had a significant impact on mOS: 13m (95% CI 10-15) for wild-type (WT) vs 31.6 m (95% CI 16-46) for mutant (MUT), p=0.01, HR=0.32. Survival probability was higher at 12, 24, and 48m for WT vs MUT (57% vs 81%, 17% vs 70%, and 6% vs 37%). SF3B1 mutation was not statistically associated with any clinical variable. In the multivariate analysis using all clinical variables and SF3B1 status, only DFS ≥2y (HR=2.3), elevated LDH (HR=3.5), elevated ALP (HR=6.1), and SF3B1 MUT (HR=0.2, 95%CI 0.1-0.8, p=0.02) remained significant.
Conclusions
SF3B1 mutation is independently associated with improved OS in MUM patients. Results may affect MUM care, treatment development, and trial stratification. More research is needed to confirm these findings.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1150P - Transforming growth factor-beta-1 and soluble co-inhibitory immune checkpoints as putative drivers of immune suppression in advanced basal cell carcinoma
Presenter: Bernardo Rapoport
Session: Poster session 13
1151P - Characteristics and treatment outcomes in cutaneous adnexal carcinomas
Presenter: Adam Rock
Session: Poster session 13
1152P - Association of immune-related adverse events (irAE) requiring glucocorticoids (GCs) with outcome and biomarkers in advanced cutaneous malignant melanoma (CMM) treated with immune checkpoint inhibitors (ICI)
Presenter: Fernanda Costa Svedman
Session: Poster session 13
1153P - Incidence and characteristics of immunotherapy related adrenal insufficiency in a monocenter, pan-cancer cohort of 4314 patients
Presenter: Minke Lucas
Session: Poster session 13
1154P - Thromboembolic events in patients with melanoma receiving immune checkpoint inhibitors: Incidence and risk factors
Presenter: Daan van Dorst
Session: Poster session 13
1155P - Application of novel machine learning to predict immunotherapy related toxicities for metastatic melanoma patients from baseline 18F-FDG PET/CT scans
Presenter: Roslyn Francis
Session: Poster session 13
1156P - Immune-related adverse events in a nationwide cohort of melanoma patients treated with adjuvant anti-PD1: Seasonal variation and association with outcome
Presenter: Eva Ellebæk
Session: Poster session 13
1157P - Corticosteroids and second-line immunosuppressants for immune-related adverse events and melanoma survival
Presenter: Rik Verheijden
Session: Poster session 13
1158P - Association of corticosteroid (CS) exposure with treatment failure in patients (pts) with advanced melanoma treated with immune checkpoint inhibitors (ICIs)
Presenter: Ha Mo Linh Le
Session: Poster session 13
1159P - Characterization of melanoma of unknown primary in the era of immunotherapy and targeted therapy in Spain: Results from the prospective real-world study GEM 1801
Presenter: Pablo Cerezuela-Fuentes
Session: Poster session 13