Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination
Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination
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DOI：
10.1097/cmr.0000000000000386
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发表时间：
2017-10-01
影响因子：
2.2
通讯作者：
Meyer, Nicolas
中科院分区：
文献类型：
--
作者：
Aboudaram, Amelie;Modesto, Anouchka;Meyer, Nicolas
免疫检查点抑制剂和放射治疗（RT）的组合代表了一种有前途的治疗策略，部分由远位效应介导，但与这种组合相关的临床经验仍然很少。回顾性收集了所有连续接受程序性死亡1（PD-1）免疫检查点抑制剂治疗的转移性黑色素瘤患者的临床数据和治疗模式。比较了接受同步放疗（IR）或不接受放疗（NIR）的患者的生存数据、最佳总体缓解以及急性和迟发毒性（根据不良事件通用术语标准，v 4.3分级）。2014年8月至2015年12月期间，59例患者在我们的机构接受了抗PD-1免疫治疗[pembrolizumab（n=28）或nivolumab（n=31）]。其中，29%（n=17）接受姑息性RT共21个部位，平均剂量为30戈伊，分10次输送。两组的急性和晚期毒性特征相似。中位随访10个月后，IR组的客观缓解率（完全或部分缓解）显著高于NIR组（64.7% vs. 33.3%，P=0.02），RT后1例完全缓解者与远位效应一致。NIR组与IR组的6个月无病生存率和总生存率分别为49.7%与64.7%（P=0.32）和58.8%与76.4%（P=0.42）。我们在这里报告说，RT和抗PD-1免疫疗法的组合耐受性良好，并导致照射野内外的肿瘤缓解率显著提高，这是第一个报告的实体瘤远位效应病例所强调的。版权所有（C）2017威科医疗集团All rights reserved.
A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4.3) were compared between patients receiving concurrent RT (IR) or no irradiation (NIR). Fifty-nine patients received anti-PD-1 immunotherapy [pembrolizumab (n=28) or nivolumab (n=31)] between August 2014 and December 2015 at our institution. Among these, 29% (n=17) received palliative RT for a total of 21 sites, with a mean dose of 30 Gy delivered in 10 fractions. Acute and late toxicity profiles were similar in the two groups. After a 10-month median follow-up, the objective response rate (complete or partial response) was significantly higher in the IR group versus the NIR group (64.7 vs. 33.3%, P=0.02) and one complete responder after RT was compatible with an abscopal effect. The 6-month disease-free survival and overall survival rates for the NIR group versus the IR group were 49.7 versus 64.7% ( P=0.32) and 58.8 versus 76.4% (P=0.42), respectively. We report here that the combination of RT and anti-PD-1 immunotherapy is well tolerated and leads to a significant higher tumor response rate within and outside the irradiated field, which is emphasized by the first reported case of an abscopal effect in solid tumors. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.