Yuki Akihiko, Takenouchi Tatsuya, Takatsuka Sumiko, Ishiguro Takuro
aDivision of Dermatology, Niigata University Graduate School of Medical and Dental Sciences Departments of bDermatology cInternal Medicine, Niigata Cancer Center Hospital, Niigata, Japan.
Melanoma Res. 2017 Dec;27(6):635-637. doi: 10.1097/CMR.0000000000000392.
Nivolumab is an antibody against programmed cell death 1 and functions as an immune checkpoint inhibitor for various malignancies, including unresectable melanomas. Nivolumab causes several immune-related adverse events, which typically include skin rash, pneumonitis, thyroid dysfunction, hepatitis, and colitis; in rare cases, anemia may be present. There are several reports of autoimmune hemolytic anemia that has developed in response to nivolumab; however, there are few reports of pure red cell aplasia (PRCA). We describe a patient who developed PRCA during nivolumab administration. A 70-year-old Japanese woman received nivolumab for cardiac metastasis from malignant melanoma from an unknown site. Twenty-one months after nivolumab administration (31 courses), treatment was discontinued because she developed severe anemia. Blood test results indicated normocytic, normochromic anemia, and reticulocytopenia, but all other components were normal. Bone marrow aspiration showed increased megakaryocytes and decreased erythroblasts; these findings were consistent with PRCA. Anemia improved without recurrence after treatment with corticosteroids and blood transfusions. The steroid dosage was reduced gradually, and to date, the patient has not experienced recurrence of anemia. The tumor decreased in size and the patient has shown a continued response to treatment with decrease in disease for 3 years. Although it is unclear how nivolumab causes PRCA, hematological toxicities have been reported in patients treated with immunotherapy drugs. PRCA might be an unrecognized immune-mediated adverse event that did not manifest during the clinical trial phase.
纳武单抗是一种抗程序性细胞死亡蛋白1的抗体，可作为多种恶性肿瘤的免疫检查点抑制剂，包括不可切除的黑色素瘤。纳武单抗会引发多种免疫相关不良事件，通常包括皮疹、肺炎、甲状腺功能障碍、肝炎和结肠炎；在罕见情况下，可能会出现贫血。有几篇关于纳武单抗引发自身免疫性溶血性贫血的报道；然而，关于纯红细胞再生障碍性贫血（PRCA）的报道很少。我们描述了一名在接受纳武单抗治疗期间发生PRCA的患者。一名70岁的日本女性因不明部位的恶性黑色素瘤心脏转移接受纳武单抗治疗。在接受纳武单抗治疗21个月（31个疗程）后，由于出现严重贫血，治疗中断。血液检查结果显示为正细胞正色素性贫血和网织红细胞减少，但其他所有指标均正常。骨髓穿刺显示巨核细胞增多，成红细胞减少；这些发现与PRCA一致。经皮质类固醇和输血治疗后，贫血改善且未复发。类固醇剂量逐渐减少，迄今为止，患者未出现贫血复发。肿瘤体积缩小，患者对治疗持续有反应，疾病缓解达3年。虽然尚不清楚纳武单抗如何导致PRCA，但免疫治疗药物治疗的患者中已报告有血液学毒性。PRCA可能是一种在临床试验阶段未表现出来的未被认识的免疫介导不良事件。
