807P Adjuvant anti-PD-1 monotherapy benefit varies across different ethnicities and melanoma subtypes

Abstract

Although anti-programmed cell death receptor-1 (PD-1) monotherapy is a standard adjuvant treatment for melanoma patients underwent definitive surgery, their efficacy is evaluated mostly in Caucasians and cutaneous melanoma, it remains unclear in other ethnic groups and melanoma subtypes. Clinical data for patients (pts) with resected stage II/III/IV melanoma treated with anti-PD-1 monotherapy both in and outside clinical trial settings between 2015 and 2021 was collected retrospectively from 6 independent institutions in the US, Australia, Japan and China. Survival outcomes (both recurrence free survival [RFS] and overall survival [OS]) were compared by ethnicity (Caucasian versus East-Asian/African) and by different melanoma subtypes (non-acral-cutaneous[NAC]/unknown primary[UP], acral and mucosal). In total 537 pts were included. Caucasians had significantly longer RFS and OS. Among different melanoma subtypes, NAC/UP had the best RFS and OS, followed by acral. Mucosal melanoma had the poorest survival outcomes. In NAC/UP subtypes, Caucasians had longer RFS (with significance) and OS (with marginal significance) than East Asian/African. In the multivariate analysis incorporating ethnicity, melanoma subtype, age, sex, stage, LDH, and BRAF mutation status, Caucasian ethnicity was independently correlated with significantly better RFS (HR 0.59; 95%CI 0.41-0.84; P=.004) and a trend towards better OS (HR 0.59, 95%CI 0.34-1.02; P=.06), while mucosal subtype independently associated with both poorer RFS (HR 2.43; 95%CI 1.55-3.80; P<.001) and OS (HR 2.97; 95%CI, 1.53-5.78; P=.001).Table: 807PEntire CohortNAC/UP subtypesEthnicityMel SubtypeEthnicityCaucasianEast-Asian /AfricanNAC/UPAcralMucosalCaucasianEast-Asian /African(n=262)(n=275)(n=352)(n=83)(n=102)(n=246)(n=106)RFS1-y rate (%, 95% CI)80 (76-86)67 (62-73)77 (73-82)79 (70-88)58 (49-69)81 (76-86)68 (60-78)2-y rate (%, 95% CI)70 (64-76)49 (44-56)66 (61-71)57 (46-70)40 (32-52)71 (65-77)53 (44-64)P value<.001<.001<.001OS2-y rate (%, 95% CI)92 (88-95)80 (75-86)90 (87-94)83 (74-92)75 (67-85)92 (89-96)85 (78-93)4-y rate (%, 95% CI)83 (78-89)55 (46-66)82 (77-87)57 (38-86)46 (36-60)84 (78-90)78 (69-88)P value<.001<.001.07 Open table in a new tab Ethnicity and melanoma subtype both contribute to survival discrepancies in melanoma patients undergoing adjuvant anti-PD-1 monotherapy. The somatic genetic and immunologic underpinning of these differences remain unclear and warrants further investigation.