Harvard Medical School, Boston, Massachusetts.
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Cancer Med. 2019 Sep;8(11):4986-4999. doi: 10.1002/cam4.2397. Epub 2019 Jul 9.
Immune checkpoint inhibitors (CPIs) have revolutionized oncologic therapy but can lead to immune-related adverse events (irAEs). Corticosteroids are first-line treatment with escalation to biologic immunosuppression in refractory cases. CPI-related gastroenterocolitis (GEC) affects 20%-50% of patients receiving CPIs and can carry significant morbidity and mortality. Severe CPI-related GEC is not well-described. We present the clinical characterization of all CPI-related GEC requiring admission at a single institution.
Clinical, laboratory, radiographic, and endoscopic data were extracted from charts of all melanoma patients ≥18 years of age admitted to one institution for CPI-related GEC, from February 5, 2011 to December 13, 2016. Patients were followed until December 31, 2017 for further admissions. Survival, outcomes, and pharmaceutical-use analyses were performed.
Median time-to-admission from initial CPI exposure was 73.5 days. Median length of stay was 4.5 days. About 50.0% required second-line immunosuppression. Readmission for recrudescence occurred in 33.3%. Common Terminology Criteria for Adverse Events (CTCAE) grade was not significantly associated with outcomes. Hypoalbuminemia (P = 0.005), relative lymphopenia (P = 0.027), and decreased lactate dehydrogenase (P = 0.026) were associated with second-line immunosuppression. There was no difference in progression-free survival (PFS) or OS (P = 0.367, 0.400) for second-line immunosuppression. Subgroup analysis showed that early corticosteroid administration (P = 0.045) was associated with decreased PFS.
Severe CPI-related GEC typically manifests within 3 months of immunotherapy exposure. Rates of second-line immunosuppression and readmission for recrudescence were high. CTCAE grade did not capture the degree of severity in our cohort. Second-line immunosuppression was not associated with poorer oncologic outcomes; however, early corticosteroid exposure was associated with decreased PFS. Further investigation is warranted.
免疫检查点抑制剂（CPIs）彻底改变了肿瘤治疗方法，但可导致免疫相关不良反应（irAEs）。皮质类固醇是一线治疗药物，在难治性病例中可升级为生物免疫抑制治疗。CPIs 相关性结肠炎（GEC）影响 20%-50%接受 CPIs 治疗的患者，可导致严重发病率和死亡率。严重 CPI 相关性 GEC 尚未得到充分描述。我们报道了单一机构收治的所有需要住院治疗的 CPI 相关性 GEC 患者的临床特征。
从 2011 年 2 月 5 日至 2016 年 12 月 13 日，从一家机构收治的所有年龄≥18 岁的黑色素瘤患者的图表中提取了与 CPI 相关性 GEC 相关的临床、实验室、影像学和内镜数据。患者随访至 2017 年 12 月 31 日，以了解进一步的入院情况。进行了生存、结局和药物使用分析。
从首次 CPI 暴露到住院的中位时间为 73.5 天。中位住院时间为 4.5 天。约 50.0%需要二线免疫抑制治疗。33.3%的患者因病情复发而再次入院。常见不良事件术语标准（CTCAE）分级与结局无显著相关性。低白蛋白血症（P=0.005）、相对淋巴细胞减少症（P=0.027）和乳酸脱氢酶降低（P=0.026）与二线免疫抑制治疗相关。二线免疫抑制治疗在无进展生存期（PFS）或总生存期（OS）方面无差异（P=0.367，0.400）。亚组分析显示，早期使用皮质类固醇（P=0.045）与 PFS 降低相关。
严重 CPI 相关性 GEC 通常在免疫治疗暴露后 3 个月内出现。二线免疫抑制治疗和因病情复发而再次入院的发生率较高。在我们的队列中，CTCAE 分级并未捕捉到严重程度。二线免疫抑制治疗与较差的肿瘤学结局无关；然而，早期皮质类固醇暴露与 PFS 降低有关。需要进一步研究。
