Fournier Marie, Mortier Laurent, Dereure Olivier, Dalac Sophie, Oriano Bastien, Dalle Stéphane, Lebbé Céleste
Université de Paris Cité, AP-HP Hôpital Saint-Louis, Dermatology Department, Paris, France.
CHRU de Lille, Dermatology Department, Lille, France.
Eur J Cancer. 2023 Nov;193:113289. doi: 10.1016/j.ejca.2023.113289. Epub 2023 Aug 11.
The definition of hyperprogressive disease (HPD) is controversial in the literature and has not been widely described in melanoma. The aim of this study was to determine whether the concept of HPD applies to patients treated for advanced melanoma, using a definition with a simple, reproducible criterion, and to determine whether it is possible to identify predictive factors for HPD.
This was a retrospective analysis on a prospective cohort. The data were extracted from MelBase, a French prospective, multicentre cohort of adult patients with advanced melanoma. The patients, following informed consent, were treated prospectively with anti-PD1, ipilimumab+nivolumab, BRAF/MEKi, or chemotherapy, 1st line or thereafter. HPD was defined, within 3 months following the start of the treatment, with the help of a clinical and biological criterion using Response Evaluation Criteria in Solid Tumours, Eastern Cooperative Oncology Group Performance Score, and lactate dehydrogenase.
The occurrence of HPD in the 4 groups was as follows (numbers of patients out of the total number): anti-PD1 98/1004 (10%), ipilumumab +nivolumab 19/327 (6%), targeted therapy 31/751 (4%), and chemotherapy 40/397 (10%). In the anti programmed cell death protein 1 (APD1) group, the relevant risk factors for HPD were: more than 3 metastatic sites (p = 0.03) and liver metastasis (p < 0.001).
This data, thanks to relevant clinical and biological criteria feasible in daily practice, supports the presence of a subgroup whose disease deteriorates rapidly during mono-immunotherapy. Also observed with other treatments, HPD could be the consequence of a natural and aggressive evolution of the disease, alleviated by strong-acting treatments.
高进展性疾病（HPD）的定义在文献中存在争议，在黑色素瘤中尚未得到广泛描述。本研究的目的是使用一个简单、可重复的标准定义，确定HPD的概念是否适用于晚期黑色素瘤患者，并确定是否有可能识别HPD的预测因素。
这是一项对前瞻性队列的回顾性分析。数据从MelBase中提取，MelBase是一个法国的前瞻性、多中心成年晚期黑色素瘤患者队列。患者在获得知情同意后，接受抗程序性死亡蛋白1（anti-PD1）、伊匹木单抗+纳武单抗、BRAF/MEK抑制剂或化疗，一线或后续治疗。在治疗开始后的3个月内，借助实体瘤疗效评价标准、东部肿瘤协作组体能状态评分和乳酸脱氢酶，通过临床和生物学标准定义HPD。
4组中HPD的发生率如下（患者人数/总数）：抗程序性死亡蛋白1（anti-PD1）组98/1004（10%），伊匹木单抗+纳武单抗组19/327（6%），靶向治疗组31/751（4%），化疗组40/397（10%）。在抗程序性死亡蛋白1（APD1）组中，HPD的相关危险因素为：转移部位超过3个（p = 0.03）和肝转移（p < 0.001）。
这些数据借助日常实践中可行的相关临床和生物学标准，支持存在一个在单药免疫治疗期间疾病迅速恶化的亚组。在其他治疗中也观察到，HPD可能是疾病自然且侵袭性进展的结果，强效治疗可缓解。
