Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia, USA.
J Immunother Cancer. 2024 Oct 26;12(10):e010116. doi: 10.1136/jitc-2024-010116.
Immune checkpoint blockade (ICB) therapies are one of the greatest advances in the history of cancer care and are now commonly used in the management of many different malignancies. However, much remains unknown about the factors that affect the efficacy and side effect profile of these agents. This review delves into the published literature that evaluates the intricate interplay between race, age, gender, and social determinants in shaping outcomes following ICB across solid tumors and hematologic malignancies. We examine the pivotal phase 2 and 3 trials to evaluate the demographics of participants and outcomes based on these variables, if reported. Most, but not all, trials reported some basic demographic information like age, sex, race, ethnicity, and/or geographic area for enrollment. Clinically relevant biological markers that could affect ICB outcomes such as obesity or markers of social determinants of health were largely not reported. Trials were generally representative for men and women based on expected prevalence for a given malignancy, but often under-represented non-white participants and rarely enrolled patients from the global south. Subgroup analyses were conducted in many ICB trials for solid malignancies, but rarely conducted for hematologic malignancies. These analyses largely showed similar qualitative benefit across subgroups, but adverse events were rarely reported by subgroup. This review adds to our understanding of the populations that these clinical trials have studied and highlight the urgent need to redouble our efforts at increasing the diversity of the population in future ICB trials.
免疫检查点阻断 (ICB) 疗法是癌症治疗史上的重大进展之一,目前已广泛用于多种不同恶性肿瘤的治疗。然而,对于影响这些药物疗效和副作用的因素,仍有许多未知之处。本综述深入探讨了已发表的文献,评估了种族、年龄、性别和社会决定因素在影响 ICB 治疗实体瘤和血液恶性肿瘤的结果方面的复杂相互作用。我们检查了关键的 2 期和 3 期临床试验,以评估根据这些变量报告的参与者的人口统计学数据和结果。大多数(但不是全部)试验报告了一些基本的人口统计学信息,如年龄、性别、种族、民族和/或入组的地理区域。对 ICB 结果可能有影响的临床相关生物标志物,如肥胖或健康社会决定因素的标志物,在很大程度上未被报告。基于给定恶性肿瘤的预期流行率,试验通常在男性和女性中具有代表性,但往往代表性不足,非白人参与者较少,很少从全球南方招募患者。许多 ICB 治疗实体瘤的试验进行了亚组分析,但很少在血液恶性肿瘤中进行。这些分析主要表明亚组之间存在相似的定性益处,但很少按亚组报告不良事件。本综述增加了我们对这些临床试验所研究人群的了解,并强调迫切需要加倍努力,在未来的 ICB 试验中增加人群的多样性。