那他珠单抗治疗抗Hu相关副肿瘤性神经系统综合征的II期试验。
Phase II trial of natalizumab for the treatment of anti-Hu associated paraneoplastic neurological syndromes.
作者信息
Bastiaansen Anna E M, de Jongste Adriaan H C, de Bruijn Marienke A A M, Crijnen Yvette S, Schreurs Marco W J, Verbeek Marcel M, Dumoulin Daphne W, Taal Walter, Titulaer Maarten J, Sillevis Smitt Peter A E
机构信息
Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Department of Neurology, Elisabeth Tweesteden Medical Center, Tilburg, The Netherlands.
出版信息
Neurooncol Adv. 2021 Sep 28;3(1):vdab145. doi: 10.1093/noajnl/vdab145. eCollection 2021 Jan-Dec.
BACKGROUND
Paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS) have a very poor prognosis: more than half of the patients become bedridden and median survival is less than 12 months. Several lines of evidence suggest a pathogenic T cell-mediated immune response. Therefore, we conducted a prospective open-label phase II trial with natalizumab.
METHODS
Twenty Hu-PNS patients with progressive disease were treated with a maximum of three monthly natalizumab cycles (300 mg). The primary outcome measure was functional improvement, this was defined as at least one point decrease in modified Rankin Scale (mRS) score at the last treatment visit. In addition, treatment response was assessed wherein a mRS score ≤3 after treatment was defined as treatment responsive.
RESULTS
The median age at onset was 67.8 years (SD 8.4) with a female predominance ( = 17, 85%). The median time from symptom onset to Hu-PNS diagnosis was 5 months (IQR 2-11). Most patients had subacute sensory neuronopathy ( = 15, 75%), with a median mRS of 4 at baseline. Thirteen patients had a tumor, all small cell lung cancer. After natalizumab treatment, two patients (10%) showed functional improvement. Of the remaining patients, 60% had a stable functional outcome, while 30% showed further deterioration. Treatment response was classified as positive in nine patients (45%).
CONCLUSIONS
Natalizumab may ameliorate the disease course in Hu-PNS, but no superior effects above other reported immunosuppressive and immunomodulatory were observed. More effective treatment modalities are highly needed.
TRIAL REGISTRATION
https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000675-13/NL.
背景
伴有抗Hu抗体的副肿瘤性神经系统综合征（Hu-PNS）预后极差：超过半数患者卧床不起，中位生存期不足12个月。多项证据提示存在致病性T细胞介导的免疫反应。因此，我们开展了一项使用那他珠单抗的前瞻性开放标签II期试验。
方法
20例病情进展的Hu-PNS患者接受了最多3个每月一次的那他珠单抗疗程（300mg）治疗。主要结局指标为功能改善，定义为末次治疗访视时改良Rankin量表（mRS）评分至少降低1分。此外，评估治疗反应，治疗后mRS评分≤3定义为治疗有反应。
结果
发病时的中位年龄为67.8岁（标准差8.4），女性占优势（n = 17，85%）。从症状出现到Hu-PNS诊断的中位时间为5个月（四分位间距2-11）。多数患者患有亚急性感觉神经元病（n = 15，75%），基线时mRS中位数为4。13例患者患有肿瘤，均为小细胞肺癌。那他珠单抗治疗后，2例患者（10%）显示功能改善。其余患者中，60%功能结局稳定，而30%显示进一步恶化。9例患者（45%）的治疗反应分类为阳性。
结论
那他珠单抗可能改善Hu-PNS的病程，但未观察到优于其他报道的免疫抑制和免疫调节治疗的效果。迫切需要更有效的治疗方式。
试验注册
https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000675-13/NL
Zotero 插件