Immune checkpoint inhibitor (ICI) therapy improves outcomes in several cancers. Unfortunately, many patients experience grade 3–4 treatment-related adverse events, including gastrointestinal (GI) toxicities which are common. These GI immune-related adverse events (irAEs) induced by ICIs present significant clinical challenges, require prompt intervention, and result in treatment delays or discontinuations. The treatment for these potentially severe and even fatal GI irAEs which include enterocolitis, severe diarrhea, and hepatitis may interfere with the anti-cancer approach. Sargramostim (glycosylated, yeast-derived, recombinant human GM-CSF) is an agent that has been used in clinical practice for more than 30 years with a well-recognized safety profile and has been studied in many therapeutic areas. The mechanism of action of sargramostim may treat moderate-to-severe GI irAEs without impairing the anti-cancer therapy. Some early data also suggest a potential survival benefit. Through the differentiation/maturation of monocytes, macrophages, and neutrophils and induction of anti-inflammatory T cell responses, GM-CSF aids in GI homeostasis, mucosal healing, and mucosal immunity. GM-CSF knockout mice are susceptible to severe colitis which was prevented with murine GM-CSF administration. For some patients with GI mucosa and immune cell function impairment, e.g., Crohn’s disease, sargramostim reduces disease severity. In a prospective, randomized study (ECOG 1608), advanced melanoma patients had a reduction in grade 3–5 GI irAEs and less frequent colonic perforation in the sargramostim plus ipilimumab arm compared to ipilimumab alone. Sargramostim continues to be studied with ICIs for the prophylactic management of irAEs while also potentially providing a survival benefit.
免疫检查点抑制剂（ICI）疗法改善了多种癌症的治疗效果。然而，许多患者会出现3-4级治疗相关不良事件，其中胃肠道毒性较为常见。这些由ICI引发的胃肠道免疫相关不良事件（irAEs）带来了显著的临床挑战，需要及时干预，并常导致治疗延迟或中断。针对肠炎、严重腹泻和肝炎等可能危及生命的胃肠道irAEs的治疗，可能会干扰抗癌治疗进程。 沙格司亭（糖基化酵母源重组人GM-CSF）是一种在临床实践中应用超过30年的药物，其安全性已得到广泛认可，并在多个治疗领域进行了研究。沙格司亭的作用机制可能在不影响抗癌治疗的前提下，治疗中重度胃肠道irAEs。早期数据还提示其可能带来生存获益。通过促进单核细胞、巨噬细胞和中性粒细胞的分化/成熟，并诱导抗炎性T细胞反应，GM-CSF有助于维持胃肠道稳态、促进黏膜愈合和增强黏膜免疫。GM-CSF基因敲除小鼠易发生严重结肠炎，而给予鼠源GM-CSF可预防该病症。对于存在胃肠道黏膜和免疫细胞功能受损的患者（如克罗恩病），沙格司亭可降低疾病严重程度。 在一项前瞻性随机研究（ECOG 1608）中，与单用伊匹木单抗相比，晚期黑色素瘤患者在沙格司亭联合伊匹木单抗治疗组中，3-5级胃肠道irAEs发生率降低，结肠穿孔发生率减少。目前沙格司亭与ICI联合应用的研究仍在继续，旨在探索其对irAEs的预防性管理作用，同时可能为患者提供生存获益。
肿瘤(癌症)患者之家