Zenatri Morgan, Collins Michael, Alberto Tifanie, Farina Antonio, Collardeau-Frachon Sophie, Saint-Jean Mélanie, Bocquet François, Dumont Frederic, Honnorat Jérôme, Joubert Bastien, Raimbourg Judith
Department of Medical Oncology, Institut de Cancérologie de L'Ouest, 44805, Saint Herblain, France.
Nantes Université, Univ Angers, INSERM, CNRS, CRCI2NA, 44000, Nantes, France.
Cancer Immunol Immunother. 2025 Jan 3;74(2):45. doi: 10.1007/s00262-024-03901-4.
Immune checkpoint inhibitors (ICI), i.e., anti-PD1/PDL1 and anti-CTLA-4, have reshaped the prognosis of many cancers. Increased use of ICI has led to the onset of new adverse events. Neurological immune-related adverse events are rare, heterogenous, and potentially life-threatening. Chronic intestinal pseudo-obstruction (CIPO) is an immune-related autonomic plexus neuropathy that may be caused by infiltration of the myenteric plexus by CD8 + T cells. It is a rare and potentially fatal side effect that can be difficult to diagnose early because of initial nonspecific clinical presentation including vomiting, nausea, diarrhea, and constipation. Some rare cases have been described in the literature reporting a frequent resistance to corticosteroids making it necessary to use other immunosuppressive therapy. Vedolizumab is an antibody (Ab) blocking integrin α4-β7 used to treat inflammatory bowel disease. We report the first three cases of ICI-induced CIPO-treated with vedolizumab after corticosteroid failure, with very limited benefits (only one patient with transitory improvement). Based on our results in three cases, vedolizumab does not currently appear to be a therapeutic option. Earlier administration with a standardized dose and frequency schedule may provide better outcomes.
免疫检查点抑制剂（ICI），即抗程序性死亡蛋白1（PD1）/程序性死亡配体1（PDL1）和抗细胞毒性T淋巴细胞相关蛋白4（CTLA-4），已经重塑了许多癌症的预后。ICI使用的增加导致了新的不良事件的出现。神经免疫相关不良事件罕见、异质性强且可能危及生命。慢性肠道假性梗阻（CIPO）是一种免疫相关的自主神经丛神经病变，可能由CD8 + T细胞浸润肌间神经丛引起。它是一种罕见且可能致命的副作用，由于最初的临床表现不具有特异性，包括呕吐、恶心、腹泻和便秘，因此早期可能难以诊断。文献中描述了一些罕见病例，报告称对皮质类固醇常常耐药，因此有必要使用其他免疫抑制疗法。维多珠单抗是一种阻断整合素α4-β7的抗体（Ab），用于治疗炎症性肠病。我们报告了首例三例ICI诱导的CIPO病例，在皮质类固醇治疗失败后使用维多珠单抗治疗，获益非常有限（只有一名患者有短暂改善）。基于我们三例病例的结果，维多珠单抗目前似乎不是一种治疗选择。采用标准化剂量和给药频率更早给药可能会带来更好的结果。
