Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1466, Houston, TX, 77030, USA.
Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cancer Res Clin Oncol. 2023 Aug;149(10):7793-7803. doi: 10.1007/s00432-023-04736-9. Epub 2023 Apr 8.
Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of certain cancers but cause immune-related adverse events (irAEs). Gastrointestinal irAEs may necessitate extended periods of steroid use and the initiation of selective immunosuppressive therapy (SIT) which could theoretically counteract the effect of ICIs. In this study, we aim to explore the impact of immunosuppression use and duration on cancer progression and progression-free survival (PFS).
This is a single-center retrospective review exploring cancer outcomes in patients taking ICIs who developed gastrointestinal irAEs within 1 year of ICI initiation. Cancer outcome and progression free survival (PFS) were measured and compared by using IBM SPSS Statistics 26.
Of the 116 patients included in this study, 69 received immunosuppression to treat irAEs. The occurrence of colitis and use of immunosuppression for colitis were associated with less cancer progression by later assessment (p < 0.05). Shorter durations of steroids with or without SIT for colitis were associated with less cancer progression within the study window than no immunosuppression (p < 0.05). Immunosuppression has no effect on PFS (p < 0.05).
Our study reported shorter duration of steroid treatment for colitis may be associated with less cancer progression. Though the use of immunosuppression was not found to impact PFS, this may be confounded by the presence of colitis, which is known to improve cancer outcomes and could mask any negative impact of immunosuppression on survival. It may be preferable to limit long-term immunosuppression in the treatment of immune-mediated colitis to minimize potential complications. Prospective studies are needed to clarify this relationship, and treatments that abrogate the need for immunosuppression in these patients such as fecal microbiota transplantation.
免疫检查点抑制剂（ICIs）越来越多地用于治疗某些癌症，但会引起免疫相关不良反应（irAEs）。胃肠道 irAEs 可能需要长期使用类固醇和启动选择性免疫抑制治疗（SIT），这可能会在理论上抵消 ICI 的作用。在这项研究中，我们旨在探讨免疫抑制的使用和持续时间对癌症进展和无进展生存期（PFS）的影响。
这是一项单中心回顾性研究，探讨了在 ICI 启动后 1 年内发生胃肠道 irAEs 的接受 ICI 治疗的患者的癌症结局。使用 IBM SPSS Statistics 26 测量和比较癌症结局和无进展生存期（PFS）。
在这项研究中，纳入了 116 名患者，其中 69 名患者因 irAEs 接受了免疫抑制治疗。结肠炎的发生和使用免疫抑制剂治疗结肠炎与后期评估时癌症进展较少有关（p<0.05）。与未使用免疫抑制剂相比，在研究窗内，类固醇治疗结肠炎的持续时间较短或同时使用 SIT 与较少的癌症进展有关（p<0.05）。免疫抑制对 PFS 没有影响（p<0.05）。
我们的研究报告称，治疗结肠炎的类固醇治疗持续时间较短可能与癌症进展较少有关。尽管免疫抑制的使用并未发现对 PFS 有影响，但这可能因结肠炎的存在而受到干扰，已知结肠炎可改善癌症结局并掩盖免疫抑制对生存的任何负面影响。在治疗免疫介导的结肠炎时，可能最好限制长期免疫抑制，以最大程度地减少潜在的并发症。需要前瞻性研究来阐明这种关系，以及能够消除这些患者对免疫抑制需求的治疗方法，例如粪便微生物群移植。
