鉴于免疫检查点抑制剂（ICI）在癌症治疗中的广泛应用，我们遇到了各种与免疫相关的不良事件（irAE），包括与免疫相关的血液嗜酸性粒细胞增多。嗜酸性粒细胞增多症被证明是 ICI 有益临床反应的潜在阳性预测标志物。然而，有报道称嗜酸性粒细胞诱发的不良事件（Eo-irAE）伴有器官功能障碍，需要开始口服糖皮质激素治疗并停止 ICI。我们的目的是评估白细胞介素 (IL) 5 轴抑制在 Eo-irAE 中的疗效和安全性。继发于 ICI 治疗的 irAE。我们介绍了三例 Eo-irAE 病例，这些病例转诊至哈达萨希伯来大学医学中心的过敏和临床免疫学部门，接受帕博利珠单抗和纳武单抗（针对程序性细胞死亡 1 (PD-1) 受体的单克隆抗体）治疗后，针对两例黑色素瘤和一例转移性非小细胞肺癌。在知情同意和委员会批准后，两名患者接受了 1-3 剂美泊利珠单抗 (100mg) 单克隆 IgG1 kappa 抗 IL-5 抗体治疗，一名患者接受了最新 9 剂贝那利珠单抗 (30mg) 单克隆抗体治疗针对白细胞介素 5 受体 α 链的 IgG1 kappa 抗体，均皮下注射。对患者进行仔细随访，并通过体检和实验室测试评估治疗反应。治疗后 8-12 个月观察到 2300-8000 K/UL 水平的嗜酸性粒细胞增多，并伴有呼吸困难、关节痛、肌痛、筋膜炎、“硬斑病”症状样病变、疲劳、腹部不适、瘙痒和胸痛。 ICI 终止并没有改善症状，两名患者对糖皮质激素耐药，因此开始生物治疗以抑制 IL5 轴。患者表现出快速的临床反应，外周血嗜酸性粒细胞水平下降，症状长期缓解。没有任何负面影响的信号，例如 IL5 轴抑制后肿瘤进展。ICI 治疗继发的嗜酸性粒细胞增多可导致器官功能障碍。停止 ICI 可能无效，并且类固醇治疗可能难以缓解症状，因此应考虑靶向抑制 IL5 轴。© 作者（或其雇主）2024。CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Given the broad implementation of immune checkpoint inhibitors (ICI) for cancer therapy, we encounter a variety of immune-related adverse events (irAE) including immune-related blood eosinophilia. Eosinophilia demonstrated a potential positive predictive marker for a beneficial clinical response to ICI. However, there are reports of eosinophil-induced adverse events (Eo-irAE) with organ dysfunction requiring initiation of oral glucocorticoid therapy and discontinuation of ICI.We aim to assess the efficacy and safety of interleukin (IL) 5-axis inhibition in Eo-irAE secondary to ICI therapy.We present three cases of Eo-irAE referred to our allergy and clinical immunology unit at Hadassah Hebrew University Medical Center following therapy with pembrolizumab and nivolumab, monoclonal antibodies that target the programmed cell death 1 (PD-1) receptor, for two cases of melanoma and one metastatic non-small cell lung carcinoma. Following informed consent and committee approval, two patients were treated with 1-3 doses of mepolizumab, 100 mg, monoclonal IgG1 kappa anti-IL-5 antibody, and one patient received up-to-date 9 doses of benralizumab, 30 mg, monoclonal IgG1 kappa antibody directed against the alpha chain of the interleukin-5 receptor, both administered subcutaneously. Patients were carefully followed and treatment response was assessed by physical examinations and laboratory tests.Hypereosinophilia at the level of 2300-8000 K/UL was observed 8-12 months following therapy accompanied by symptoms of dyspnea, arthralgia, myalgia, fasciitis, 'morphea'-like lesions, fatigue, abdominal discomfort, pruritus, and chest pain. ICI discontinuation did not improve symptoms, two patients were resistant to glucocorticoids and therefore biological treatment was initiated to inhibit the IL5 axis. Patients demonstrated rapid clinical response and a decrease in peripheral blood eosinophil levels with long-term symptoms remission. There were no signals of negative impacts, such as tumor progression following IL5 axis inhibition.Eosinophilia secondary to ICI therapy can lead to organ dysfunction. Discontinuation of ICI might not be effective and symptoms may be refractory to steroid therapy hence targeted inhibition of the IL5 axis should be considered.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.