Anti-PD-1 matches interferon as adjuvant therapy for acral melanoma: a retrospective study.

Background: Programmed cell death protein (PD-1) inhibitors constitute the standard adjuvant therapy for cutaneous melanoma (CM), but well-established strategies for acral melanoma (AM) remain limited.

Objective: To compare the efficacy of adjuvant anti-PD-1 immunotherapy versus high-dose interferon α-2b (HDI) in patients with stage IIB-IV AM and CM.

Design: This multicenter, retrospective study enrolled 511 patients with resected stage IIB-IV AM and CM between January 2017 and December 2023.

Methods: Patients were divided into four groups by subtype and treatment: patients with CM and treated with anti-PD-1 (CM-PD-1), patients with CM and treated with HDI (CM-HDI), patients with AM and treated with anti-PD-1 (AM-PD-1), and patients with AM and treated with HDI (AM-HDI). Recurrence-free survival (RFS), overall survival (OS), and patient safety were evaluated.

Results: This study comprised 362 AM and 149 CM cases. AM cases presented with thicker primary lesions, higher ulceration rates, and fewer BRAF mutations. Median follow-up was 49 months. Among patients with stage IIB/C, median RFS was not reached in any groups. Among stage III/IV patients, median RFS was 14.6 (CM-PD-1), 13.7 (CM-HDI), 13.3 (AM-PD-1), and 11.7 months (AM-HDI), and median OS was 61.6, 40.7, 42.4, and 53.4 months, respectively, without significant intergroup differences. Anti-PD-1 significantly improved RFS in patients with stage III/IV AM with KIT mutations (9.1 vs 5.0 months, p = 0.048) and ⩾4 lymph node metastases (10.5 vs 6.6 months, p = 0.036). Anti-PD-1 had significantly fewer adverse effects than HDI (60.4% vs 88.6%, p < 0.001), including fewer grades 3-4 events (4.6% vs 30.7%, p < 0.001).

Conclusion: Adjuvant anti-PD-1 therapy provides RFS comparable to that of HDI in AM and CM, with a superior safety profile. Patients with AM harboring KIT mutations derive greater benefits from adjuvant anti-PD-1 therapy.