University of Chicago, Chicago, IL.
ICON plc, Raleigh, NC.
J Clin Oncol. 2022 Dec 10;40(35):4107-4118. doi: 10.1200/JCO.21.02478. Epub 2022 Jul 15.
Postconsolidation immunotherapy including dinutuximab, granulocyte-macrophage colony-stimulating factor, and interleukin-2 improved outcomes for patients with high-risk neuroblastoma enrolled on the randomized portion of Children's Oncology Group study ANBL0032. After random assignment ended, all patients were assigned to immunotherapy. Survival and toxicities were assessed.
Patients with a pre-autologous stem cell transplant (ASCT) response (excluding bone marrow) of partial response or better were eligible. Demographics, stage, tumor biology, pre-ASCT response, and adverse events were summarized using descriptive statistics. Event-free survival (EFS) and overall survival (OS) from time of enrollment (up to day +200 from last ASCT) were evaluated.
From 2009 to 2015, 1,183 patients were treated. Five-year EFS and OS for the entire cohort were 61.1 ± 1.9% and 71.9 ± 1.7%, respectively. For patients ≥ 18 months old at diagnosis with International Neuroblastoma Staging System stage 4 disease (n = 662) 5-year EFS and OS were 57.0 ± 2.4% and 70.9 ± 2.2%, respectively. EFS was superior for patients with complete response/very good partial response pre-ASCT compared with those with PR (5-year EFS: 64.2 ± 2.2% 55.4 ± 3.2%, = .0133); however, OS was not significantly different. Allergic reactions, capillary leak, fever, and hypotension were more frequent during interleukin-2-containing cycles than granulocyte-macrophage colony-stimulating factor-containing cycles ( < .0001). EFS was superior in patients with higher peak dinutuximab levels during cycle 1 ( = .034) and those with a high affinity FCGR3A genotype ( = .0418). Human antichimeric antibody status did not correlate with survival.
Analysis of a cohort assigned to immunotherapy after cessation of random assignment on ANBL0032 confirmed previously described survival and toxicity outcomes. EFS was highest among patients with end-induction complete response/very good partial response. Among patients with available data, higher dinutuximab levels and FCGR3A genotype were associated with superior EFS. These may be predictive biomarkers for dinutuximab therapy.
巩固性免疫治疗包括丁酸钠、粒细胞-巨噬细胞集落刺激因子和白细胞介素-2，改善了入组儿童肿瘤学组研究 ANBL0032 随机部分的高危神经母细胞瘤患者的结局。随机分组结束后，所有患者均接受免疫治疗。评估生存和毒性。
符合条件的患者为自体干细胞移植（ASCT）前（不包括骨髓）部分缓解或更好的反应。使用描述性统计方法总结人口统计学、分期、肿瘤生物学、ASCT 前反应和不良事件。从入组时间（最后一次 ASCT 后最多 200 天）评估无事件生存（EFS）和总生存（OS）。
2009 年至 2015 年，共有 1183 例患者接受治疗。整个队列的 5 年 EFS 和 OS 分别为 61.1±1.9%和 71.9±1.7%。对于诊断时年龄≥18 个月且国际神经母细胞瘤分期系统（INSS）分期为 4 期的患者（n=662），5 年 EFS 和 OS 分别为 57.0±2.4%和 70.9±2.2%。ASCT 前完全缓解/很好部分缓解患者的 EFS 优于 PR 患者（5 年 EFS：64.2±2.2% 55.4±3.2%， =.0133），但 OS 无显著差异。白细胞介素-2 周期中的过敏反应、毛细血管渗漏、发热和低血压比粒细胞集落刺激因子周期更频繁（<.0001）。第 1 周期中 dinutuximab 水平较高的患者（=.034）和高亲和力 FCGR3A 基因型的患者（=.0418）的 EFS 更高。人抗嵌合抗体状态与生存无关。
对 ANBL0032 随机分组结束后分配至免疫治疗的队列进行分析，证实了先前描述的生存和毒性结局。诱导结束时完全缓解/很好部分缓解患者的 EFS 最高。在有可用数据的患者中，较高的丁酸钠水平和 FCGR3A 基因型与较高的 EFS 相关。这些可能是丁酸钠治疗的预测生物标志物。
