Jacob Jake S, Dutra Barbara E, Garcia-Rodriguez Victor, Panneerselvam Kavea, Abraham Fiyinfoluwa O, Zou Fangwen, Ma Weijie, Grivas Petros, Thompson John A, Altan Mehmet, Oliva Isabella C Glitza, Zhang Hao Chi, Thomas Anusha S, Wang Yinghong
1Department of Internal Medicine, Baylor College of Medicine, Houston, Texas.
2Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas.
J Natl Compr Canc Netw. 2021 Aug 4;19(12):1415-1424. doi: 10.6004/jnccn.2020.7697.
Immune checkpoint inhibitor (ICI) therapy predisposes patients to immune-related adverse events (irAEs). Data are limited regarding the incidence, management, and outcomes of one such irAE: mucositis. In this study, we evaluated the clinical characteristics, disease course, treatment, and outcomes of ICI-mediated mucositis.
This was a retrospective, single-center study of patients who received ICI therapy and developed oral mucositis at The University of Texas MD Anderson Cancer Center from January 2009 to September 2019. Inclusion criteria included age ≥18 years, a diagnosis of oral mucositis and/or stomatitis based on ICD-9 and ICD-10 codes, and therapy using CTLA-4 or PD-1/L1 inhibitors alone or combined with other agents.
We identified 152 patients with a mean age of 60 years, 51% of whom were men. Of the sample patients, 73% had stage IV cancer, with melanoma the most common (28%). Median time from ICI initiation to mucositis was 91 days. The most common clinical presentation of mucositis was odynophagia and/or oral pain (89%), 91% developed CTCAE grade 1-2 mucositis, and 78% received anti-PD-1/L1 monotherapy. Compared with anti-PD-1/L1-based therapy, anti-CTLA-4-based therapy was more frequently associated with earlier onset of mucositis (73 vs 96 days; P=.077) and a lower rate of symptom resolution (76% vs 92%; P=.029); 24% of patients required immunosuppressive therapy, which was associated with longer symptom duration (84 vs 34 days; P=.002) and higher mucositis recurrence rate (61% vs 32%; P=.006). ICI interruption was associated with worse survival (P=.037). Mucositis recurrence, immunosuppressant use, and presence of other irAEs did not affect survival.
For ICI-mediated mucositis, a diagnosis of exclusion has not been well recognized and is understudied. Although the clinical symptoms of mucositis are mostly mild, approximately 25% of patients require immunosuppression. Mucositis recurrence can occur in approximately 39% patients. Our results showed that ICI interruption compromises overall survival.
免疫检查点抑制剂（ICI）治疗使患者易发生免疫相关不良事件（irAE）。关于其中一种irAE——口腔炎的发病率、管理及结局的数据有限。在本研究中，我们评估了ICI介导的口腔炎的临床特征、病程、治疗及结局。
这是一项回顾性单中心研究，研究对象为2009年1月至2019年9月在德克萨斯大学MD安德森癌症中心接受ICI治疗并发生口腔炎的患者。纳入标准包括年龄≥18岁、根据ICD - 9和ICD - 10编码诊断为口腔炎和/或口腔炎，以及单独使用CTLA - 4或PD - 1/L1抑制剂或与其他药物联合使用的治疗。
我们确定了152例患者，平均年龄60岁，其中51%为男性。在样本患者中，73%患有IV期癌症，最常见的是黑色素瘤（28%）。从开始使用ICI到发生口腔炎的中位时间为91天。口腔炎最常见的临床表现是吞咽痛和/或口腔疼痛（89%），91%发生CTCAE 1 - 2级口腔炎，78%接受抗PD - 1/L1单药治疗。与基于抗PD - 1/L1的治疗相比，基于抗CTLA - 4的治疗更常与口腔炎更早发作（73天对96天；P = 0.077）和症状缓解率较低（76%对92%；P = 0.029）相关；24%的患者需要免疫抑制治疗，这与症状持续时间较长（84天对34天；P = 0.002）和口腔炎复发率较高（61%对32%；P = 0.006）相关。中断ICI与较差的生存率相关（P = 0.037）。口腔炎复发、免疫抑制剂使用及其他irAE的存在不影响生存率。
对于ICI介导的口腔炎，排除性诊断尚未得到充分认识且研究不足。尽管口腔炎的临床症状大多较轻，但约25%的患者需要免疫抑制治疗。约39%的患者可能发生口腔炎复发。我们的结果表明，中断ICI会损害总生存期。
