Berti Alvise, Cavalli Giulio, Guglielmi Barbara, Biavasco Riccardo, Campochiaro Corrado, Tomelleri Alessandro, Nicoletti Roberto, Panzacchi Andrea, Ferrarini Marina, Dagna Lorenzo
Unit of Immunology, Rheumatology, Allergy and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Oncoimmunology. 2017 Apr 20;6(6):e1318237. doi: 10.1080/2162402X.2017.1318237. eCollection 2017.
Treatment of Erdheim-Chester disease (ECD), a rare non-Langerhans histiocytosis, relies on interferon-α, chemotherapeutic agents such as purine analogs, cytokine-blocking agents and BRAF inhibitors. Since interleukin (IL)-6 levels are elevated in serum and lesions of ECD patients, we evaluated the therapeutic efficacy and safety of IL-6 blockade with tocilizumab. We conducted an open-label, single-arm, phase II, prospective study of tocilizumab in three patients with multisystem ECD and poor tolerance/contraindications to IFN-α. Modifications of symptoms attributed to ECD represented the criteria for evaluation of clinical response. Changes at positron emission tomography scan, computed tomography scan, and magnetic resonance imaging at month 6 represented the main criteria for the evaluation of radiological response. Sustained complete clinical response and partial radiological improvement were observed in two patients, paralleled by modulation of systemic pro-inflammatory mediators. In spite of disease stabilization or improvement at extra-neurological sites, a third patient experienced a radiologic and clinical progression of central nervous system involvement, mirrored by a dramatic increase of circulating IL-6 and related cytokines. These findings indicate that IL-6 inhibition can be effective in ECD, but caution is advisable in patients with neurologic involvement. IL-6 emerges as a central mediator in ECD pathogenesis.
Erdheim-Chester病（ECD）是一种罕见的非朗格汉斯组织细胞增多症，其治疗依赖于干扰素-α、嘌呤类似物等化疗药物、细胞因子阻断剂和BRAF抑制剂。由于ECD患者血清和病变组织中的白细胞介素（IL）-6水平升高，我们评估了托珠单抗阻断IL-6的治疗效果和安全性。我们对三名多系统ECD且对干扰素-α耐受性差/有禁忌证的患者进行了一项开放标签、单臂、II期前瞻性托珠单抗研究。将归因于ECD的症状改善作为评估临床反应的标准。第6个月时正电子发射断层扫描、计算机断层扫描和磁共振成像的变化作为评估影像学反应的主要标准。两名患者观察到持续的完全临床反应和部分影像学改善，同时全身促炎介质得到调节。尽管神经外部位的疾病稳定或改善，但第三名患者出现中枢神经系统受累的影像学和临床进展，同时循环IL-6和相关细胞因子显著增加。这些发现表明，IL-6抑制在ECD中可能有效，但对于有神经受累的患者建议谨慎使用。IL-6成为ECD发病机制中的核心介质。
