作为护理标准的免疫检查点抑制剂(ICIs)彻底改变了转移性黑色素瘤患者的治疗。与单独的单一疗法相比,纳武单抗和伊匹单抗的组合提高了治疗功效并延长了生存期。然而,联合治疗也与不良事件发生率增加相关.我们报告了一个罕见但重要的多器官功能衰竭患者单剂量纳武单抗联合ipilimumab。2021年2月25日,一名患有溃疡性结肠炎缓解期和转移性黑色素瘤病史的60岁男性因假定的脓毒症入院。出现中性粒细胞减少性发热后。他的脑转移先前于2021年1月14日切除,并开始使用地塞米松4mgBID治疗六周。2021年2月11日,他接受了一剂nivolumab加ipilimumab,根据CheckMate-067协议。14天后他出现发烧,腹泻,全血细胞减少症,肾功能衰竭,药物性肝炎,和心肌炎.传染性检查是阴性的。他的中性粒细胞减少症对生长因子有反应。由于免疫疗法和皮质类固醇治疗,他被诊断为间质性肾炎。他的症状随着肾脏的改善而缓解,肝,和心脏功能。他在稳定的情况下出院回家。尽管这些特异性免疫相关不良事件(irAEs)并不常见且很少同时发生,ICI可以触发非特异性免疫系统激活,导致广泛的炎症作用。由于irAE会导致多器官衰竭,正如在这个案例中所证明的,早期识别和建立大剂量类固醇对于防止快速恶化至关重要.鉴于ICI治疗是几种癌症的标准治疗方法,并且经常在临床试验中进行研究,有必要增加对irAE毒性的教育,并更新发热癌症患者的管理算法.
Immune checkpoint inhibitors (ICIs) as standard of care have revolutionized the treatment of patients with metastatic melanoma. The combination of nivolumab and ipilimumab improves treatment efficacy and prolongs survival compared to monotherapy alone. However, combination therapy is also associated with an increased incidence of adverse events. We report an uncommon yet important
case of multi-organ failure in a patient following a single dose of nivolumab plus ipilimumab. A 60-year-old male with a history of ulcerative colitis in remission and metastatic melanoma was admitted on February 25, 2021, for presumed sepsis, after presenting with neutropenic fever. His brain metastases were previously resected on January 14, 2021, and he was started on dexamethasone 4 mg BID for six weeks. On February 11, 2021, he received one dose of nivolumab plus ipilimumab, per the CheckMate-067 protocol. He presented 14 days later with fever, diarrhea, pancytopenia, renal failure, drug-induced hepatitis, and myocarditis. The infectious workup was negative. His neutropenia responded to growth factors. He was diagnosed with interstitial nephritis due to immunotherapy and treated with corticosteroids. His symptoms resolved with concomitant improvement of his renal, hepatic, and cardiac function. He was discharged home in a stable condition. Although these specific immune-related adverse events (irAEs) are uncommon and rarely occur simultaneously, ICIs can trigger non-specific immune system activation, resulting in widespread inflammatory effects. Since irAEs can lead to multi-organ failure, as evidenced in this
case, early recognition and institution of high-dose steroids are critical to preventing rapid deterioration. Given that ICI therapy is the standard of care for several cancers and is often studied in clinical trials, increased education on irAE toxicity and updated algorithms on the management of febrile cancer patients are warranted.