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Updated: Dec 18, 2025
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients
Y Nakamura1, K Namikawa2, K Yoshino3
1Department of Skin Oncology/Dermatology, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Saitama, Japan.
Background:
Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM.
Patients And Methods:
We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies.
Results:
In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03).
Conclusions:
Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.
Insights
Anti-programmed cell death 1 (anti-PD-1) antibodies show limited efficacy in advanced acral melanoma (AM). Patients with nail apparatus melanoma experienced poorer outcomes, suggesting a need for novel combination therapies.
Area of Science:
- Oncology
- Immunotherapy
- Dermatology
Background:
- Acral melanoma (AM) is a distinct subtype of melanoma.
- AM is underrepresented in clinical immunotherapy trials.
- Limited data exists on anti-programmed cell death 1 (anti-PD-1) efficacy in AM.
Purpose of the Study:
- To analyze the efficacy of anti-PD-1 antibodies in advanced acral melanoma.
- To evaluate response rates, survival, and toxicity in AM patients treated with anti-PD-1 therapy.
Main Methods:
- Retrospective evaluation of unresectable stage III or IV AM patients treated with anti-PD-1 antibodies.
- Data collected from 21 Japanese institutions (2014-2018).
- Analysis included clinicobiologic characteristics, objective response rate (ORR), overall survival (OS), and toxicity.
Main Results:
- 193 patients included: 70 nail apparatus, 123 palm and sole.
- Overall ORR was 16.6%, median OS was 18.1 months.
- Nail apparatus melanoma showed significantly lower ORR (8.6% vs 21.1%) and poorer median OS (12.8 vs 22.3 months).
- Normal lactate dehydrogenase (LDH) was associated with significantly better OS (24.9 vs 10.7 months).
Conclusions:
- Anti-PD-1 antibodies demonstrate limited efficacy in advanced acral melanoma.
- Nail apparatus melanoma patients exhibit poorer response and survival outcomes.
- Nail apparatus melanoma warrants further research into novel combination therapies with immune checkpoint inhibitors.
