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Anti-PD-1 matches interferon as adjuvant therapy for acral melanoma: a retrospective study
Yu Du1, Yu Chen2, Jiaxiang Wang1
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China.
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.
Insights
Adjuvant anti-PD-1 therapy shows comparable efficacy to high-dose interferon for melanoma, with fewer side effects. Acral melanoma patients with KIT mutations benefit most from anti-PD-1 treatment.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Cutaneous melanoma (CM) adjuvant therapy standardly uses Programmed cell death protein (PD-1) inhibitors.
- Established adjuvant strategies for acral melanoma (AM) are limited.
- This study compares anti-PD-1 immunotherapy with high-dose interferon α-2b (HDI) for resected stage IIB-IV AM and CM.
Purpose of the Study:
- To compare the efficacy and safety of adjuvant anti-PD-1 immunotherapy versus HDI in patients with stage IIB-IV AM and CM.
- To evaluate recurrence-free survival (RFS), overall survival (OS), and patient safety.
- To identify specific patient subgroups that may benefit more from either treatment modality.
Main Methods:
- A multicenter, retrospective study of 511 patients with resected stage IIB-IV AM and CM.
- Patients were categorized into four groups based on melanoma subtype (AM or CM) and treatment (anti-PD-1 or HDI).
- Recurrence-free survival (RFS), overall survival (OS), and safety profiles were analyzed.
Main Results:
- No significant differences in median RFS or OS were observed between anti-PD-1 and HDI groups among stage III/IV patients.
- Anti-PD-1 therapy demonstrated a significantly better safety profile than HDI, with fewer adverse events (60.4% vs 88.6%) and grade 3-4 events (4.6% vs 30.7%).
- Stage III/IV acral melanoma patients with KIT mutations showed improved RFS with anti-PD-1 therapy (9.1 vs 5.0 months).
Conclusions:
- Adjuvant anti-PD-1 therapy offers comparable RFS to HDI in both AM and CM patients.
- Anti-PD-1 therapy presents a superior safety profile compared to HDI.
- Acral melanoma patients with KIT mutations may derive greater benefit from adjuvant anti-PD-1 therapy.
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