Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study
Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study
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DOI：
10.1016/j.annonc.2022.06.004
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发表时间：
2022-09-05
影响因子：
50.5
通讯作者：
Long, G., V
中科院分区：
文献类型：
--
作者：
Dimitriou, F.;Namikawa, K.;Long, G., V
背景：粘液性黑色素瘤（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（ICI）疗效的数据有限。我们通过主要研究中心和种族/人种分析，确定了ICI在MM中的疗效。患者和方法：在澳大利亚，欧洲，美国和亚洲的25个癌症中心进行了回顾性队列研究。组织学确诊的MM患者接受抗程序性细胞死亡蛋白1（PD-1）+/-易普利姆玛治疗。主要终点为缓解率（RR）、无进展生存期（PFS）、总生存期（OS），按主要部位（鼻-口腔、泌尿生殖、肛门直肠、其他）、种族/人种（白人、亚裔、其他）和治疗列出。进行单变量和多变量考克斯比例风险模型分析。结果：共纳入545例患者：331例（63%）白人，176例（33%）亚裔和20例（4%）其他。原发部位包括肛门直肠113例（21%）、泌尿生殖器178例（32%）、鼻口腔206例（38%）和其他45例（8%）。348例（64%）患者接受抗PD-1治疗，197例（36%）患者接受抗PD-1/易普利姆玛治疗。RR、PFS和OS在主要研究中心、种族/人种或治疗方面无差异。与抗PD-1（29%，95% CI 21%-37%）相比，抗PD-1/易普利姆玛[40%，95%置信区间（CI）29%-54%]的经鼻-经口给药RR在数值上更高。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% CI 18个月-未达到）。与PFS短相关的因素为美国东部肿瘤协作组（ECOG）体力状态（PS）≥ 3（P < 0.01）、乳酸脱氢酶（LDH）高于正常值上限（ULN）（P = 0.01）、肺转移（P < 0.01）和既往治疗≥ 1次（P < 0.01）。与短OS相关的因素为ECOG PS >= 1（P < 0.01）、LDH > ULN（P = 0.03）、肺转移（P < 0.01）和既往治疗>= 1（P < 0.01）。结论：MM预后差。抗PD-1 fipilimumab的治疗功效相似，并且不因种族/人种而不同。经鼻-经口初次给药对抗PD-1/易普利姆玛的应答在数值上更高，但生存期无差异。对于其他主要部位，添加易普利姆玛并没有显示出比抗PD-1更大的益处。在应答者中，mDoR较短，获得性耐药常见。其他因素，包括转移的部位和数量，与生存率相关。
Background: 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. Patients and methods: 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. Results: 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). Conclusions: MM has poor prognosis. Treatment efficacy of anti-PD-1 f 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.