Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients
Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients
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DOI：
10.1016/j.annonc.2020.05.031
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发表时间：
2020-09-01
影响因子：
50.5
通讯作者：
Yamazaki, N.
中科院分区：
文献类型：
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作者：
Nakamura, Y.;Namikawa, K.;Yamazaki, N.
背景资料：肢端黑色素瘤（AM）是一种流行病学和分子学上不同的实体，在黑色素瘤免疫治疗的临床试验中代表性不足。我们的目的是分析抗程序性细胞死亡1（抗PD-1）抗体在晚期AM中的疗效。患者和方法：我们回顾性评估了2014年至2018年期间在21家日本机构接受抗PD-1抗体治疗的不可切除的III期或IV期AM患者。临床生物学特征、客观缓解率（ORR，RECIST）、使用Kaplan-Meier分析估计的生存率和毒性（不良事件通用术语标准4.0）。结果：共纳入193例患者（甲器，70例;掌跖，123例）。143例患者（74.1%）使用抗PD-1抗体作为一线治疗。102例患者（52.8%）的基线乳酸脱氢酶（LDH）在正常浓度范围内。所有患者的ORR为16.6%（完全缓解3.1%;部分缓解13.5%），中位总生存期（OS）为18.1个月。LDH浓度正常与OS的相关性显著强于LDH浓度异常（中位OS为24.9个月vs 10.7个月; P < 0.001）。尽管指甲装置组与手掌和足底组的基线特征相似，但指甲装置组的ORR显著较低[6/70例患者（8.6%）vs 26/123例患者（21.1%）; P = 0.026]。此外，该组的中位OS显著较差（12.8个月对22.3个月; P = 0.03）。结论：抗PD-1抗体在AM患者中的疗效有限。值得注意的是，患有甲器黑色素瘤的患者的反应和存活率较差，使得甲器黑色素瘤成为进一步研究与免疫检查点抑制剂的新型联合疗法的有效性的强有力的候选者。
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.