Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.
Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.
复制标题
DOI：
10.1056/nejmoa0911123
复制
发表时间：
2010-09-30
期刊：
影响因子：
--
通讯作者：
Children's Oncology Group
中科院分区：
文献类型：
--
作者：
Yu AL;Gilman AL;Ozkaynak MF;London WB;Kreissman SG;Chen HX;Smith M;Anderson B;Villablanca JG;Matthay KK;Shimada H;Grupp SA;Seeger R;Reynolds CP;Buxton A;Reisfeld RA;Gillies SD;Cohn SL;Maris JM;Sondel PM;Children's Oncology Group
临床前和初步临床数据表明，ch14.18，一种抗肿瘤相关的二唾液酸神经节苷脂GD 2的单克隆抗体，具有抗神经母细胞瘤的活性，并且当ch14.18与粒细胞-巨噬细胞集落刺激因子（GM-CSF）或白细胞介素-2组合时，这种活性增强。我们进行了一项研究，以确定在强化多模式治疗后，在标准异维甲酸治疗中加入ch14.18、GM-CSF和白细胞介素-2是否会改善高危神经母细胞瘤的结局。对诱导治疗和干细胞移植有反应的高危神经母细胞瘤患者以1：1的比例随机分配接受标准治疗（6个周期的异维A酸）或免疫治疗（6个周期的异维A酸和5个周期的ch14.18联合交替GM-CSF和白细胞介素-2）。在意向治疗的基础上，比较免疫治疗组和标准治疗组的无事件生存率和总生存率。共有226名符合条件的患者被随机分配到治疗组。在免疫治疗组中，共有52%的患者出现3级、4级或5级疼痛，分别有23%和25%的患者出现毛细血管渗漏综合征和超敏反应。观察到61%的预期事件，研究符合因疗效而提前停止的标准。中位随访时间为2.1年。在无事件生存率（2年时66±5% vs. 46±5%，P = 0.01）和总生存率（2年时86±4% vs. 75±5%，P = 0.02，未对中期分析进行调整）方面，免疫治疗上级标准治疗。在高危神经母细胞瘤患者中，与标准治疗相比，ch14.18、GM-CSF和白细胞介素-2免疫治疗与显著改善的结局相关。
Preclinical and preliminary clinical data indicate that ch14.18, a monoclonal antibody against the tumor-associated disialoganglioside GD2, has activity against neuroblastoma and that such activity is enhanced when ch14.18 is combined with granulocyte–macrophage colony-stimulating factor (GM-CSF) or interleukin-2. We conducted a study to determine whether adding ch14.18, GM-CSF, and interleukin-2 to standard isotretinoin therapy after intensive multimodal therapy would improve outcomes in high-risk neuroblastoma. Patients with high-risk neuroblastoma who had a response to induction therapy and stem-cell transplantation were randomly assigned, in a 1:1 ratio, to receive standard therapy (six cycles of isotretinoin) or immunotherapy (six cycles of isotretinoin and five concomitant cycles of ch14.18 in combination with alternating GM-CSF and interleukin-2). Event-free survival and overall survival were compared between the immunotherapy group and the standard-therapy group, on an intention-to-treat basis. A total of 226 eligible patients were randomly assigned to a treatment group. In the immunotherapy group, a total of 52% of patients had pain of grade 3, 4, or 5, and 23% and 25% of patients had capillary leak syndrome and hypersensitivity reactions, respectively. With 61% of the number of expected events observed, the study met the criteria for early stopping owing to efficacy. The median duration of follow-up was 2.1 years. Immunotherapy was superior to standard therapy with regard to rates of event-free survival (66±5% vs. 46±5% at 2 years, P = 0.01) and overall survival (86±4% vs. 75±5% at 2 years, P = 0.02 without adjustment for interim analyses). Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma.