Zhou Li, Cao Min, Zhu Haibin, Chi Zhihong, Cui Chuanliang, Sheng Xinan, Mao Lili, Lian Bin, Tang Bixia, Yan Xieqiao, Bai Xue, Wang Xuan, Li Siming, Guo Jun, Sun Ying-Shi, Si Lu
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute, Haidian District, Beijing, People's Republic of China.
Oncologist. 2025 Feb 6;30(2). doi: 10.1093/oncolo/oyae211.
A minority subset of immunotherapy patients manifests hyperprogressive disease (HPD), with the disparity in melanoma subtypes yet to be reported. This study aimed to delineate the proportion and prognosis of HPD in patients receiving anti-PD-1 monotherapy and to identify patient with HPD clinical characteristics across melanoma subtypes to inform clinical decision making.
Utilizing 4 established HPD definitions, the incidence of HPD in patients with advanced melanoma on anti-PD-1 monotherapy was determined. The incidence rates and prognostic abilities of various HPD definitions were compared to elect the most effective one. This facilitated a comparative analysis of subtypes and clinical features between patients with HPD and traditional progression.
A total of 262 patients with advanced melanoma treated with anti-PD-1 monotherapy from 5 prospectively registered clinical trials were included in the study. The objective response rate (ORR) and disease control rate (DCR) was 21% and 58%, respectively, with 42% showcasing progression disease. The HPD incidences by 4 definitions were 13.2%, 16.8%, 10.8%, and 28.2%. All definitions effectively segregated HPD patients, with significantly poorer outcome than other progressive patients. The Delta TGR > 100 definition was the most indicative of a reduced overall survival, corroborated by the highest hazard ratio and statistical significance. The number of metastatic organs over 2 is a risk factor for HPD (OR = 4.18, P = .0103). Mucosal melanoma was the HPD prevalent subtype (OR = 3.13, P = .0489) in multivariable analysis, which is also indicated by RECIST criteria (P = .005).
A delta TGR exceeding 100 best identified HPD patients in the advanced melanoma population treated with anti-PD-1 monotherapy. Hyperprogression was notably prevalent in mucosal melanoma patients with multiple metastatic organs. Caution against HPD is warranted when applying anti-PD-1 monotherapy in mucosal subtype.
一小部分免疫治疗患者表现出超进展性疾病（HPD），黑色素瘤亚型之间的差异尚未见报道。本研究旨在明确接受抗PD-1单药治疗患者中HPD的比例和预后，并识别不同黑色素瘤亚型中具有HPD临床特征的患者，以指导临床决策。
利用4种既定的HPD定义，确定接受抗PD-1单药治疗的晚期黑色素瘤患者中HPD的发生率。比较各种HPD定义的发生率和预后能力，以选出最有效的定义。这有助于对HPD患者与传统进展患者的亚型和临床特征进行比较分析。
本研究纳入了来自5项前瞻性注册临床试验的262例接受抗PD-1单药治疗的晚期黑色素瘤患者。客观缓解率（ORR）和疾病控制率（DCR）分别为21%和58%，42%的患者出现疾病进展。4种定义下的HPD发生率分别为13.2%、16.8%、10.8%和28.2%。所有定义均能有效区分HPD患者，其预后明显比其他进展患者差。Delta TGR > 100定义最能表明总生存期缩短，最高风险比和统计学意义也证实了这一点。转移器官数超过2个是HPD的一个危险因素（OR = 4.18，P = .0103）。在多变量分析中，黏膜黑色素瘤是HPD的常见亚型（OR = 3.13，P = .0489），RECIST标准也表明了这一点（P = .005）。
在接受抗PD-1单药治疗的晚期黑色素瘤人群中，Delta TGR超过100最能识别HPD患者。超进展在有多个转移器官的黏膜黑色素瘤患者中尤为普遍。在黏膜亚型中应用抗PD-1单药治疗时，应警惕HPD。
