Abstract：
Anti-GD2 monoclonal antibodies (mAb) improve the prognosis of high-risk neuroblastoma (HR-NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second-line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti-GD2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long-term survival in this vulnerable age group. Thirty-three HR-NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized-3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb-related long-term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post-mAb treatments included chemotherapy, radiotherapy, and anti-NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse-free post-mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti-GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70-100 mg/m2 /cycle). HR-NB in infants proved to be highly curable.
摘要：
抗GD2单克隆抗体（mAb）可改善高危神经母细胞瘤（HR-NB）的预后。全球经验几乎只涉及幼儿和老年患者接受多模态或二线治疗后，也就是说,诊断后几个月。相比之下,在我们的中心,婴儿接受抗GD2mAb是因为这种免疫疗法在诱导化疗期间或之后立即开始.我们现在报告可行性，安全,和长期生存在这个脆弱的年龄组。33例HR-NB患者在3F8（鼠mAb;n=21）或纳西他单抗（人源化-3F8;n=12）开始时<19个月大，用30英寸到90英寸的静脉注射。患者接受了镇痛药和抗组胺药。常见的毒性（疼痛，荨麻疹,咳嗽)是可控的，允许门诊治疗。毛细管泄漏,后部可逆性脑病综合征，和mAb相关的长期毒性没有发生。两个3F8周期由于心动过缓（一种预先存在的疾病）和哮喘症状而中止，分别。一名患者因低血压而接受1/2剂量的第1天纳西他单抗;随后施用全剂量。mAb后治疗包括化疗，放射治疗,和抗NB疫苗。在3F8患者中，17/21在诊断后5.6+至24.1+(中位数13.4+)年的所有治疗完全缓解。在naxitamab患者中，10/12在诊断后1.7+至4.3+(中位数3.1+)年保持无复发mAb。短期门诊输注的毒性相似，与老年患者中这些和其他抗GD2mAb的毒性相匹配。这些发现是令人放心的，因为naxitamab的剂量比3F8，dinutuximab高>2.5倍（〜270mg/m2/周期），和二乌妥昔单抗β（70-100mg/m2/周期）。婴儿的HR-NB被证明是高度可治愈的。
