Department of Dermatology, Shinshu University School of Medicine, Matsumoto, Japan.
Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
J Dermatol. 2018 Nov;45(11):1340-1344. doi: 10.1111/1346-8138.14605. Epub 2018 Aug 25.
Along with the expansion of therapeutic options for metastatic melanoma, the development of useful biomarkers is urgently required to predict and monitor treatment response. Serum 5-S-cysteinyldopa (5-S-CD) has been identified as a diagnostic marker of malignant melanoma, but its utility as a biomarker for emerging therapeutic agents remains unknown. We assessed serum 5-S-CD in 12 metastatic melanoma patients (median age, 76 years; six men and six women) who had been treated with nivolumab (Nivo) at Shinshu University Hospital between 2014 and 2016. Serum 5-S-CD and lactate dehydrogenase levels before and at 3-6 weeks of Nivo treatment were obtained and their changes were compared with clinical responses as defined by the Response Evaluation Criteria in Solid Tumors criteria (version 1.1). A decrease of 10 nmol/L or more of serum 5-S-CD was observed only in partial response patients (2/3 cases, 67%), while an increase of 10 nmol/L or more of serum 5-S-CD was witnessed only in progressive disease patients (4/8 cases, 50%). Serum 5-S-CD changes were within ±10 nmol/L in the remaining six patients (partial response, one; stable disease, one; progressive disease, four). The results of the four moderately affected progressive disease patients were suspected to have been influenced by small-sized metastatic lesions, a mixed response that included diminished and enlarged metastatic lesions, prior therapy to Nivo with BRAF inhibitors or radiation, or the development of brain metastasis. Serum 5-S-CD in the early phase of Nivo treatment may be helpful to predict therapeutic response in metastatic melanoma.
随着转移性黑色素瘤治疗选择的扩大，迫切需要开发有用的生物标志物来预测和监测治疗反应。血清 5-S-半胱氨酸（5-S-CD）已被确定为恶性黑色素瘤的诊断标志物，但作为新兴治疗药物的生物标志物的用途尚不清楚。我们评估了 2014 年至 2016 年间在信州大学医院接受纳武单抗（Nivo）治疗的 12 例转移性黑色素瘤患者（中位年龄 76 岁；男 6 例，女 6 例）的血清 5-S-CD。在 Nivo 治疗前和 3-6 周时获得血清 5-S-CD 和乳酸脱氢酶水平，并将其变化与实体瘤反应评估标准（版本 1.1）定义的临床反应进行比较。仅在部分缓解患者（2/3 例，67%）中观察到血清 5-S-CD 降低 10 nmol/L 或更多，而在进展性疾病患者（4/8 例，50%）中仅观察到血清 5-S-CD 增加 10 nmol/L 或更多。在其余 6 例患者（部分缓解 1 例，稳定疾病 1 例，进展性疾病 4 例）中，血清 5-S-CD 变化在±10 nmol/L 范围内。对 4 例中度进展性疾病患者的结果怀疑受到小转移病灶的影响，包括减少和增大的转移病灶的混合反应、Nivo 治疗前接受 BRAF 抑制剂或放疗、或脑转移的发生。Nivo 治疗早期的血清 5-S-CD 可能有助于预测转移性黑色素瘤的治疗反应。
