Barbacki Ariane, Maliha Peter G, Hudson Marie, Small David
Departments of Internal Medicine.
Nuclear Medicine.
Anticancer Drugs. 2018 Sep;29(8):817-819. doi: 10.1097/CAD.0000000000000661.
Immune checkpoint inhibitors have revolutionized cancer therapy. Given their mechanism of action, immune-related adverse events have been associated with their use. We present the first documented case of pembrolizumab-induced grade IV neutropenia. A 73-year-old women known for myositis, Crohn's disease, and hypothyroidism and diagnosed with PD-L1 positive stage IV pulmonary adenocarcinoma is treated with Pembrolizumab. She develops grade IV neutropenia 2 weeks after her second infusion. She is therefore hospitalized and treated initially with corticosteroids, granulocyte colony-stimulating factor, and intravenous immunoglobulins. Given the persistent neutropenia, cyclosporine was added, but quickly stopped owing to fever. The patient recovered her neutrophils 6.5 weeks after her initial Pembrolizumab infusion and 12 days after admission. She has been subsequently successfully tapered off steroids with no recurrence after 3 months of follow-up. This is the first case of grade IV neutropenia secondary to Pembrolizumab. This case is of particular interest given the patient's pre-existing autoimmune history. Treatment of severe neutropenia due to other PD1 inhibitors has generally consisted of steroids, granulocyte colony-stimulating factor, intravenous immunoglobulins, mycophenolate mofetil, cyclosporine A, and anti-thymocyte globulins - though the benefits of immunosuppression are not clear and may be harmful given the infectious risks. Large studies are required to clarify the spectrum and optimal management of immune-related adverse events and overall risk/benefits of immune checkpoint inhibitors in patients with pre-existing autoimmunity.
免疫检查点抑制剂彻底改变了癌症治疗方式。鉴于其作用机制，使用该药物会引发免疫相关不良事件。我们报告了首例有记录的派姆单抗诱发的IV级中性粒细胞减少症病例。一名73岁女性，患有肌炎、克罗恩病和甲状腺功能减退症，被诊断为PD-L1阳性的IV期肺腺癌，接受派姆单抗治疗。在第二次输注后2周，她出现了IV级中性粒细胞减少症。因此，她住院治疗，最初使用了皮质类固醇、粒细胞集落刺激因子和静脉注射免疫球蛋白。鉴于中性粒细胞减少症持续存在，加用了环孢素，但因发热很快停药。患者在首次输注派姆单抗后6.5周以及入院后12天中性粒细胞恢复正常。随后，她成功逐渐减少了类固醇用量，随访3个月后未复发。这是首例继发于派姆单抗的IV级中性粒细胞减少症病例。鉴于患者既往有自身免疫病史，该病例尤为引人关注。对于其他PD1抑制剂所致的严重中性粒细胞减少症，治疗通常包括使用类固醇、粒细胞集落刺激因子、静脉注射免疫球蛋白、霉酚酸酯、环孢素A和抗胸腺细胞球蛋白——尽管免疫抑制的益处尚不清楚，而且鉴于感染风险可能有害。需要开展大型研究以明确免疫相关不良事件的范围和最佳管理方法，以及免疫检查点抑制剂在已有自身免疫性疾病患者中的总体风险/获益情况。
