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e21516 Background: The clinical efficacy of PD-1 inhibitors as an adjuvant treatment for Asian melanoma patients has not yet been determined. Methods: Thus, this single-centre, retrospective study analysed the clinical data of 90 Chinese patients with completely resected, stage III cutaneous or acral melanoma who received either adjuvant PD-1 inhibitor or high-dose interferon α-2b (HDI). Propensity score matching (PSM) was used to control baseline differences between the two treatment groups. The primary end point was recurrence-free survival (RFS), and the secondary end points included distance metastasis-free survival (DMFS) and incidence of first distant metastatic sites. Results: Anti-PD-1 treatment resulted in significantly longer RFS (18-month RFS, 53.3% versus 26.7%; 95% CI, 0.097-0.975; P < 0.05) and DMFS (18-month DMFS, 70.9% versus 46.1%; 95% CI, 0.13-0.945; P < 0.05) than HDI in cutaneous melanoma patients. However, adjuvant anti-PD-1 treatment had no advantage over HDI in acral melanoma patients (18-month RFS, 30.0% versus 35.9%; P > 0.05; 18-month DMFS, 36.5% versus 63.6%; P > 0.05). The incidence of lung metastasis at first in the anti-PD-1 group was found to be significantly lower (12.5% versus 48.5%; P < 0.05) in cutaneous melanoma patients than in acral melanoma patients, but no difference in metastatic sites were observed between the two treatment groups among acral melanoma patients. The incidence of treatment-related AEs was similar between the two treatment groups. Conclusions: In conclusion, adjuvant anti-PD-1 treatment was well tolerated and yielded a significantly better prognosis than HDI in Chinese patients with stage IIIB/C cutaneous melanoma, but a significant difference was not observed in those with acral melanoma.

This retrospective study aimed to evaluate the combined effect of anti-PD-1 inhibitor and nanoparticle albumin-bound (nab)-paclitaxel for refractory melanoma among Chinese patients. Data from January 2018 to March 2021 were retrospectively collected and analyzed. Sixty-four patients were eligible for analysis from a single Chinese cancer center. The median follow-up was 16.0 months at data cutoff. The objective response rate (ORR) was 29.7%, and the disease control rate (DCR) was 67.2% in all patients. Treatment-naive patients had significantly higher ORR than pretreated patients (42.9% vs 13.8%, p = 0.011). Cutaneous melanoma patients with NRAS gene mutation benefited more than non-mutated patients (DCR of 100% vs. 54.5%) (p = 0.030). The median progression-free survival (mPFS) of all patients was 5.2 months and the duration of response was 10.8 months. Median duration of disease control was 7.7 months. Prior treatment-naive patients had significantly longer PFS than those who accepted prior treatments (7.2 vs. 5.1 months, p = 0.024). Patients with abnormally high LDH level had shorter mPFS (3.6 months vs. 6.6 months, p = 0.020). Median overall survival was not reached in this study. Most patients experienced adverse events (AEs), but only 17.2% of patients experienced grade 3 severe AEs. The most common AEs were alopecia (89.1%), neutropenia (18.8%), pruritus (15.6%), and arthralgia (14.1%). Some patients had immune related AEs (irAEs). No grade 4 or 5 AEs were observed. Patients with ≥ 3 AEs or with irAEs had longer mPFS (p

Background Acral and mucosal melanomas are rarely seen in Caucasians but common in China. There are limited data on the recurrence characteristics for these patients. This study aimed to identify the recurrence pattern for localized melanoma in China, especially acral and mucosal subtypes. Methods Patients with localized melanoma who underwent radical resection between January 1999 and December 2014 in southern China were retrospectively reviewed. Survival and annual recurrence hazard were analyzed by Kaplan–Meier method and hazard function, respectively. Results Totally, 1012 patients were included (acral melanoma 400; chronic sun-induced damage (CSD)/non-CSD melanoma 314; mucosal melanoma 298). Recurrence was recorded in 808 patients (localized 14.1%; regional 29.6%, and distant 56.3%). Mucosal melanoma had local and M1c stage recurrence more frequently than cutaneous melanoma, but less frequent regional node relapse. There was no difference in recurrent site distribution between acral and CSD/non-CSD melanoma. The annual recurrence hazard curve for the entire cohort showed a double-peaked pattern with the first major peak in the second year after surgery and the second peak near the seventh year. Mucosal melanoma had a higher recurrence risk than cutaneous melanoma. Acral melanoma had a lower flat recurrence peak than CSD/non-CSD melanoma. Tumor thickness > 4.0 mm, ulceration, positive regional nodes, and wound infection were associated with a higher recurrence risk in cutaneous melanoma. Adjuvant therapy reduced the recurrence risk of cutaneous melanoma but not of mucosal melanoma. Conclusions This is a large cohort about the rule of recurrence risk in acral and mucosal melanoma and will provide an initial framework for development of surveillance and adjuvant strategy for Chinese melanoma patients.

BackgroundImmune checkpoint inhibitors (ICIs) induce better tumor regression in melanoma with programmed cell death 1 ligand 1 (PD-L1) high expression, but there has been an upsurge of failed responses. In this study, we aimed to explore the additional mechanisms possibly accounting for ICIs resistance and interventional strategies to overcome the resistance in melanoma with PD-L1 high expression.MethodsMelanoma xenografts and cytotoxicity assays were used to investigate function of SOX2 in regulating antitumor immunity. The activity of the janus kinase-signal transducer and activator of transcriptions (JAK-STAT) pathway was investigated by western blots, quantitative PCR and luciferase assay. Epigenetic compounds library screen was employed to identify inhibitors that could decrease SOX2 level. The effect of histone deacetylase inhibitor SAHA in antitumor immunity alone or in combination with immunotherapy was also determined in vitro and in vivo. Prognostic impact of SOX2 was analyzed using transcriptional profiles and clinical data download from the Gene Expression Omnibus and The Cancer Genome Atlas repository.ResultsWe uncovered a role of SOX2 in attenuating the sensitivity of melanoma cells to CD8+ T-cell killing. Mechanistically, SOX2 inhibited phosphatases suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase non-receptor type 1 (PTPN1) transcription, induced duration activation of the JAK-STAT pathway and thereby overexpression of interferon stimulated genes resistance signature (ISG.RS). By targeting the SOX2-JAK-STAT signaling, SAHA promoted the antitumor efficacy of IFNγ or anti-PD-1 in vitro and in vivo. Moreover, SOX2 was an independent prognostic factor for poor survival and resistant to anti-PD-1 therapy in melanoma with PD-L1 high expression.ConclusionsOur data unveiled an additional function of SOX2 causing immune evasion of CD8+ T-cell killing through alleviating the JAK-STAT pathway and ISG.RS expression. We also provided a rationale to explore a novel combination of ICIs with SAHA clinically, especially in melanoma with PD-L1 and SOX2 high expression.

9563 Background: Treatment options for melanoma, which has the highest mutation burden among common cancers, has proliferated in the past decade. Genomic profiling has becoming essential to clinical decision making. However, limited studies have interrogated the genomic landscape of Chinese melanoma patients. We also investigated the correlation between tumor mutation burden (TMB) and clinical outcomes of immunotherapy (IO). Methods: In this study, we retrospectively surveyed the genomic profiling of primary tumors of 81 (40 males, 41 females) metastatic Chinese melanoma patients with a median age of 52, using a panel consisting of 295 cancer-related genes, spanning 2.02MB of human genome. Patients used IO as first line treatment (n = 25) were enrolled for survival analyses. Results: In this cohort, 15, 24 and 42 were acral, mucosal and cutaneous melanoma, respectively. Collectively, we identified 1,114 mutations, spanning 248 genes, with BRAF, MYC and NBN being the most frequently mutated genes, occurring in 40%, 27% and 21% of patients, respectively. Mutation spectrum varied significantly by subtypes. BRAF (57%) and LRP1B (26%) were the most frequently mutated genes in cutaneous melanoma (CM). KIT and NRAS, reported to be frequently mutated in CM, each occurred in only 12% patients in this cohort. MYC amplification was the most commonly seen mutation in acral and mucosal melanoma (MM). Other frequent mutations in MM included: NBN (38%) RUNX1T1(29%) and TP53 (29%). In acral melanoma (AM), CCND1, FGF3/19, NF1and NBN were frequently mutated. It is interesting to note that no TP53 mutation was observed in AM. AM and MM had significantly more CNVs than CM. Of the 25 patients underwent IO, our data revealed a positive correlation between TMB and PFS (p = 0.007). Such correlation also exited in each subtype. Furthermore, we derived a cutoff of 15, which can effectively distinguish clinical response. Patients with TMB > 15 mut/Mb had a significantly longer PFS than patients harboring TMB < 15 mut/Mb (P = 0.02). Patients with CM had a longer PFS than patients with AM or MM (p = 0.018). No correlation between PDL1 expression and PFS was observed. Conclusions: Our study revealed a distinctive mutation landscape for each subtype. Furthermore, we also revealed a positive correlation between TMB and PFS as well as a lack of correlation between PDL1 expression and PFS.