Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients

Abstract

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 KaplaneMeier 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 ¼ 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P ¼ 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.

Treatment of Advanced Melanoma: Past, Present and Future

“…A previous report also suggested that the ORR of anti-PD1 Abs for ALM and mucosal melanoma was lower in a Caucasian population [54]. Taken together, since the ORR of anti-PD1 Abs for advanced ALM in Japanese population was 16.6%, and the PFS and OS for the study cohort were 3.5 months and 18.2 months, respectively [55], the efficacy of anti-PD1 Abs monotherapy for advanced melanoma in the Japanese population was lower than that in the Caucasian population.…”

The efficacy of anti‐programmed cell death protein 1 therapy among patients with metastatic acral and metastatic mucosal melanoma

“…14 More recently, it has been reported across a series of predominantly retrospective studies that the ORR achieved with anti-PD-1 was 14.0-16.6% and the median overall survival (OS) was 18.2-25.8 months in AM patients, and 0-23.2% and 11.5-20.2 months for MM patients, respectively. [15][16][17][18][19][20] In contrast, in the Checkmate067 trial the ORR for nivolumab was 43.7% for all melanoma subtypes, with median PFS 6.9 months and median OS 36.9 months for CM patients. 21 Data thus far suggest that the AM and MM subtypes do not respond as robustly to anti-PD-1 therapy as CM.…”

Immune Checkpoint Inhibitors in Advanced Acral Melanoma: A Systematic Review

“…The median OS was reported to be 18.1 months, and irAEs of grades 3 to 5 occurred in 27 patients (14.0%). One patient (0.5%) died of grade 5 myasthenia gravis ( 23 ). A study conducted in America involved 50 patients with unresectable stage III or stage IV AM.…”

“…Six retrospective studies evaluated nivolumab and pembrolizumab together (14,16,(23)(24)(25)(26). A study involving 21 Japanese institutions evaluated the efficacy of anti-PD-1 antibodies in 193 advanced AM patients.…”