FDA Approval: Siltuximab for the Treatment of Patients with Multicentric Castleman Disease
FDA Approval: Siltuximab for the Treatment of Patients with Multicentric Castleman Disease
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DOI：
10.1158/1078-0432.ccr-14-1678
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发表时间：
2015-03-01
影响因子：
11.5
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Deisseroth, Albert;Ko, Chia-Wen;Pazdur, Richard
2014年4月22日，美国食品药品监督管理局（FDA）完全批准了 siltuximab（注射用SYLVANT；杨森生物技术公司）用于治疗人类免疫缺陷病毒（HIV）阴性和人类疱疹病毒8型（HHV - 8）阴性的多中心型卡斯尔曼病（MCD）患者。siltuximab是一种针对白细胞介素 - 6（IL - 6）的人 - 鼠嵌合单克隆抗体。该批准主要基于一项随机、双盲试验的结果，在该试验中，79例有症状的MCD患者按2∶1的比例被分配接受siltuximab加最佳支持治疗（BSC）或安慰剂加BSC。主要疗效终点是每组中达到持久的肿瘤和症状缓解且在至少18周内无治疗失败的患者比例。肿瘤缓解是基于使用修订后的恶性淋巴瘤疗效评价标准对计算机断层扫描（CT）进行的独立评估，症状缓解定义为研究者报告的34种MCD相关体征和症状完全缓解或稳定。siltuximab组中有34%的患者达到主要终点，而安慰剂组中无患者达到（P = 0.0012）。使用siltuximab治疗期间最常见的不良反应（与安慰剂相比发生率>10%）是瘙痒、体重增加、皮疹、高尿酸血症和上呼吸道感染。（C）2015美国癌症研究协会
On April 22, 2014, the FDA granted full approval to siltuximab (SYLVANT for injection; Janssen Biotech, Inc.), a chimeric humanmouse monoclonal antibody to IL6, for the treatment of patients with multicentric Castleman disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative. The approval was primarily based on the results of a randomized, double-blind trial in which 79 symptomatic patients with MCD were allocated (2: 1) to siltuximab plus best supportive care (BSC) or to placebo plus BSC. The primary efficacy endpoint was the proportion of patients in each arm achieving a durable tumor and symptomatic response that persisted for a minimum of 18 weeks without treatment failure. Tumor response was based on independent review of CT scans using the revised Response Criteria for Malignant Lymphoma, and symptomatic response was defined as complete resolution or stabilization of 34 MCD-related signs and symptoms as reported by the investigator. Thirty-four percent of patients in the siltuximab arm and no patients in the placebo arm met the primary endpoint (P = 0.0012). The most common adverse reactions (>10% compared with placebo) during treatment with siltuximab were pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infection. (C) 2015 AACR.