Abstract：
Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race.
A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted.
In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01).
MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.
A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted.
In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01).
MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.
摘要：
粘膜黑色素瘤（MM）是一种罕见的黑色素瘤亚型，具有独特的生物学特性和不良预后。关于免疫检查点抑制剂（ICIs）功效的数据有限。我们确定了ICIs在MM中的疗效，按主要地点和种族/种族进行分析。
一项来自澳大利亚25个癌症中心的回顾性队列研究，欧洲,在美国和亚洲进行。组织学证实的MM患者接受抗程序性细胞死亡蛋白1（PD-1）±ipilimumab治疗。主要终点是反应率（RR），无进展生存期（PFS），按主要部位划分的总生存期（OS）（鼻口，泌尿生殖系统,肛门直肠,其他),种族/种族(高加索人，亚洲人,其他）和治疗。进行单因素和多因素Cox比例风险模型分析。
总共，545例患者包括：331（63%）白种人，176（33%）亚洲和20（4%）其他。主要部位包括113（21%）肛门直肠，178（32%）泌尿生殖系统，206（38％）鼻口和45（8％）其他。三百四十八名（64％）患者接受了抗PD-1和197名（36％）抗PD-1/ipilimumab。RR,PFS和OS没有因主站点而异，种族/种族或待遇。经鼻口服的RR在数值上高于抗PD-1/ipilimumab[40%，95%置信区间（CI）29%至54%]与抗PD-1（29%，95%CI21%至37%)。最初有反应的患者中有35％进展。中位缓解持续时间（mDoR）为26个月（95％CI18个月-未达到）。与短PFS相关的因素是东部肿瘤协作组（ECOG）表现状态（PS）≥3（P<0.01），乳酸脱氢酶（LDH）高于正常上限（ULN）（P=0.01），肺转移（P<0.01）和≥1次治疗（P<0.01）。与短OS相关的因素为ECOGPS≥1(P<0.01),LDH>ULN(P=0.03),肺转移（P<0.01）和≥1次治疗（P<0.01）。
MM预后不良。抗PD-1±ipilimumab的治疗效果相似，种族/种族没有差异。鼻-口初级对抗PD-1/ipilimumab有更高的反应，没有生存差异。对于其他主要位点，添加ipilimumab并未显示出比抗PD-1更大的益处。在响应者中，mDoR短，获得性抗性普遍。其他因素,包括转移的部位和数量，与生存有关。
一项来自澳大利亚25个癌症中心的回顾性队列研究，欧洲,在美国和亚洲进行。组织学证实的MM患者接受抗程序性细胞死亡蛋白1（PD-1）±ipilimumab治疗。主要终点是反应率（RR），无进展生存期（PFS），按主要部位划分的总生存期（OS）（鼻口，泌尿生殖系统,肛门直肠,其他),种族/种族(高加索人，亚洲人,其他）和治疗。进行单因素和多因素Cox比例风险模型分析。
总共，545例患者包括：331（63%）白种人，176（33%）亚洲和20（4%）其他。主要部位包括113（21%）肛门直肠，178（32%）泌尿生殖系统，206（38％）鼻口和45（8％）其他。三百四十八名（64％）患者接受了抗PD-1和197名（36％）抗PD-1/ipilimumab。RR,PFS和OS没有因主站点而异，种族/种族或待遇。经鼻口服的RR在数值上高于抗PD-1/ipilimumab[40%，95%置信区间（CI）29%至54%]与抗PD-1（29%，95%CI21%至37%)。最初有反应的患者中有35％进展。中位缓解持续时间（mDoR）为26个月（95％CI18个月-未达到）。与短PFS相关的因素是东部肿瘤协作组（ECOG）表现状态（PS）≥3（P<0.01），乳酸脱氢酶（LDH）高于正常上限（ULN）（P=0.01），肺转移（P<0.01）和≥1次治疗（P<0.01）。与短OS相关的因素为ECOGPS≥1(P<0.01),LDH>ULN(P=0.03),肺转移（P<0.01）和≥1次治疗（P<0.01）。
MM预后不良。抗PD-1±ipilimumab的治疗效果相似，种族/种族没有差异。鼻-口初级对抗PD-1/ipilimumab有更高的反应，没有生存差异。对于其他主要位点，添加ipilimumab并未显示出比抗PD-1更大的益处。在响应者中，mDoR短，获得性抗性普遍。其他因素,包括转移的部位和数量，与生存有关。
