免疫相关肠炎患者的免疫检查点抑制和选择性免疫抑制治疗的联合应用。
Concurrent immune checkpoint inhibition and selective immunosuppressive therapy in patients with immune-related enterocolitis.
机构信息
Division of Gastroenterology, Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, MA, USA.
出版信息
J Immunother Cancer. 2023 Jun;11(6). doi: 10.1136/jitc-2023-007195.
PURPOSE
Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-related enterocolitis (irEC). We examined the effect of resumption of ICIs with or without concurrent selective immunosuppressive therapy (SIT) on rates of symptom recurrence and survival outcomes.
METHODS
This retrospective, multicenter study examined patients who were treated with ICI and developed irEC requiring SIT (infliximab or vedolizumab) for initial symptom control or to facilitate steroid tapering between May 2015 and June 2020. After symptom resolution, patients were restarted either on ICI alone or on concurrent ICI and SIT at the discretion of the treating physicians. The associations between irEC recurrence and treatment group were assessed via univariate analyses and multivariate logistic regression. Cox proportional hazards model was used for survival analysis.
RESULTS
Of the 138 included patients who required SIT for initial irEC symptom control, 61 (44.2%) patients resumed ICI without concurrent SIT (control group) and 77 (55.8%) patients resumed ICI therapy with concurrent SIT: 33 with infliximab and 44 with vedolizumab. After symptom resolution, patients in the control group were more commonly restarted on a different ICI regimen (65.6%) compared with those receiving SIT (31.2%) (p<0.001). The total number of ICI doses administered after irEC resolution and ICI resumption was similar in both groups (four to five doses). Recurrence of severe colitis or diarrhea after ICI resumption was seen in 34.4% of controls compared with 20.8% of patients receiving concurrent SIT. Concurrent SIT was associated with reduced risk of severe irEC recurrence after ICI resumption in a multivariate logistic regression model (OR 0.34; 95% CI 0.13 to 0.92; p=0.034). There was no difference in survival outcomes between patients in the control group and patients concurrently treated with SIT.
CONCLUSION
After resolution of irEC symptoms, reinitiation of ICI with concurrent SIT is safe, reduces severe irEC recurrence, and has no negative impact on survival outcomes.
目的
免疫检查点抑制剂（ICI）治疗常因免疫相关肠炎（irEC）而暂停。我们研究了恢复 ICI 治疗，同时或不伴选择性免疫抑制治疗（SIT）对症状复发率和生存结局的影响。
方法
这项回顾性多中心研究纳入了 2015 年 5 月至 2020 年 6 月期间接受 ICI 治疗并因 irEC 需要 SIT（英夫利昔单抗或维得利珠单抗）进行初始症状控制或促进类固醇减量的患者。在症状缓解后，根据治疗医生的判断，患者要么单独恢复 ICI 治疗，要么同时恢复 ICI 和 SIT。通过单因素分析和多因素逻辑回归评估 irEC 复发与治疗组之间的关系。使用 Cox 比例风险模型进行生存分析。
结果
在需要 SIT 进行初始 irEC 症状控制的 138 例患者中，61 例（44.2%）患者在不伴 SIT 的情况下恢复 ICI 治疗（对照组），77 例（55.8%）患者恢复 ICI 治疗并同时接受 SIT：33 例接受英夫利昔单抗，44 例接受维得利珠单抗。症状缓解后，对照组患者更常重新开始使用不同的 ICI 方案（65.6%），而接受 SIT 的患者（31.2%）则较少（p<0.001）。两组患者在 irEC 缓解和 ICI 恢复后接受的 ICI 剂量总数相似（4 至 5 剂）。在 ICI 恢复后，对照组中有 34.4%的患者出现严重结肠炎或腹泻复发，而同时接受 SIT 的患者有 20.8%出现该情况。在多因素逻辑回归模型中，同时接受 SIT 与 ICI 恢复后严重 irEC 复发风险降低相关（OR 0.34；95%CI 0.13 至 0.92；p=0.034）。在对照组患者和同时接受 SIT 治疗的患者之间，生存结局无差异。
结论
irEC 症状缓解后，同时恢复 ICI 和 SIT 是安全的，可降低严重 irEC 复发风险，且对生存结局无负面影响。
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