Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-Cis-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission
Murine Anti-GD2 Monoclonal Antibody 3F8 Combined With Granulocyte-Macrophage Colony-Stimulating Factor and 13-Cis-Retinoic Acid in High-Risk Patients With Stage 4 Neuroblastoma in First Remission
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DOI：
10.1200/jco.2011.41.3807
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发表时间：
2012-09-10
影响因子：
45.3
通讯作者：
Modak, Shakeel
中科院分区：
文献类型：
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作者：
Cheung, Nai-Kong V.;Cheung, Irene Y.;Modak, Shakeel
目的抗GD 2单克隆抗体（MoAb）联合粒细胞-巨噬细胞集落刺激因子（GM-CSF）对神经母细胞瘤（NB）有较好的治疗作用。预后变量，可能会影响临床outcome.Patients和MethodsOne六百六十九名儿童诊断为第4期NB（1988年至2008年）被纳入连续抗GD 2鼠单克隆抗体3F 8 +/- GM-CSF +/-13-顺式维甲酸（CRA）协议后，实现首次缓解（完全缓解/非常好的部分缓解）。入组方案A的患者（n = 43例高风险[HR]患者）接受3F 8单药治疗;方案B（n = 41例HR患者），干细胞移植（SCT）后，3F 8+静脉GM-CSF + CRA; C组（n = 85），SCT后3F 8+皮下GM-CSF + CRA，46/85，而85例中有28例需要额外的诱导治疗，并被认为是超高风险（UHR）。采用定量逆转录聚合酶链反应检测骨髓微小残留病（MRD）。生存概率计算的Kaplan-Meier法，预后变量进行了分析，多变量考克斯回归model.ResultsAt 5年的免疫治疗开始，无进展生存期（PFS）从44%的HR患者接受方案A的56%和62%，分别为那些接受方案B和C。总生存率（OS）分别为49%、61%和81%。UHR患者的PFS和OS分别为36%和75%。复发主要发生在孤立部位。独立的不良预后因素包括UHR（PFS）和第2周期后MRD（PFS和OS），而改善结局的预后因素是缺失杀伤免疫球蛋白样受体配体（PFS和OS），人抗小鼠抗体应答（OS），结论单中心连续临床试验的回顾性分析表明，单克隆抗体3F 8 + GM-CSF + CRA对化疗有效。耐药骨髓MRD。它对长期生存的积极影响只能通过随机研究来明确证实。
PurposeAnti-GD2 monoclonal antibody (MoAb) combined with granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown efficacy against neuroblastoma (NB). Prognostic variables that could influence clinical outcome were explored.Patients and MethodsOne hundred sixty-nine children diagnosed with stage 4 NB (1988 to 2008) were enrolled onto consecutive anti-GD2 murine MoAb 3F8 +/- GM-CSF +/- 13-cis-retinoic acid (CRA) protocols after achieving first remission (complete remission/very good partial remission). Patients enrolled in regimen A (n = 43 high-risk [HR] patients) received 3F8 alone; regimen B (n = 41 HR patients), 3F8 + intravenous GM-CSF + CRA, after stem-cell transplantation (SCT); and regimen C (n = 85), 3F8 + subcutaneous GM-CSF + CRA, 46 of 85 after SCT, whereas 28 of 85 required additional induction therapy and were deemed ultra high risk (UHR). Marrow minimal residual disease (MRD) was measured by quantitative reverse transcription polymerase chain reaction. Survival probability was calculated by the Kaplan-Meier method, and prognostic variables were analyzed by multivariate Cox regression model.ResultsAt 5 years from the start of immunotherapy, progression-free survival (PFS) improved from 44% for HR patients receiving regimen A to 56% and 62% for those receiving regimens B and C, respectively. Overall survival (OS) was 49%, 61%, and 81%, respectively. PFS and OS of UHR patients were 36% and 75%, respectively. Relapse was mostly at isolated sites. Independent adverse prognostic factors included UHR (PFS) and post-cycle two MRD (PFS and OS), whereas the prognostic factors for improved outcome were missing killer immunoglobulin-like receptor ligand (PFS and OS), human antimouse antibody response (OS), and regimen C (OS).ConclusionRetrospective analysis of consecutive trials from a single center demonstrated that MoAb 3F8 + GM-CSF + CRA is effective against chemotherapy-resistant marrow MRD. Its positive impact on long-term survival can only be confirmed definitively by randomized studies.