Mora Jaume, Castañeda Alicia, Gorostegui Maite, Santa-María Vicente, Garraus Moira, Muñoz Juan Pablo, Varo Amalia, Perez-Jaume Sara, Mañe Salvador
Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, Barcelona, Spain.
Pediatr Blood Cancer. 2021 Oct;68(10):e29121. doi: 10.1002/pbc.29121. Epub 2021 May 22.
Naxitamab is a humanized anti-disialoganglioside (GD2) monoclonal antibody approved for treatment of bone/bone marrow refractory high-risk neuroblastoma (HR-NB). Compassionate use (CU) expanded access program at Hospital Sant Joan de Deu permitted treatment of patients in complete remission (CR). We here report the survival, toxicity, and relapse pattern of patients in first or second CR treated with naxitamab and sargramostim (GM-CSF).
Seventy-three consecutive patients with HR-NB (stage M at age >18 months or MYCN-amplified stages L1/L2 at any age) were treated in first or second CR. Treatment comprised five cycles of subcutaneous (SC) GM-CSF for 5 days at 250 μg/m /day (days -4 to 0), followed by naxitamab + SC GM-CSF for 5 days at 500 μg/m /day (days 1-5). Naxitamab was infused over 30 minutes at 3 mg/kg/day, days 1, 3, and 5, outpatient.
Fifty-five patients were in first CR and 18 in second CR. Seventeen patients had MYCN-amplified NB and 11 detectable minimal residual disease in the bone marrow. Fifty-eight (79.5%) patients completed therapy. Four (5%) experienced grade 4 toxicities and 10 (14%) early relapse. Three-year event-free survival (EFS) 58.4%, 95% CI = (43.5%, 78.4%) and overall survival (OS) 82.4%, 95% CI = (66.8%, 100%). First CR patients 3-year EFS 74.3%, 95% CI = (62.7%, 88.1%), and OS 91.6%, 95% CI = (82.4%, 100%). EFS is significantly different between first and second CR (p = .0029). The pattern of relapse is predominantly (75%) of an isolated organ, mainly bone (54%). Univariate Cox models show prior history of relapse as the only statistically significant predictor of EFS but not OS.
Consolidation with naxitamab and GM-CSF resulted in excellent survival rates for HR-NB patients in CR.
纳昔妥单抗是一种人源化抗双唾液酸神经节苷脂（GD2）单克隆抗体，已被批准用于治疗骨/骨髓难治性高危神经母细胞瘤（HR-NB）。Sant Joan de Deu医院的同情用药（CU）扩大准入计划允许对完全缓解（CR）的患者进行治疗。我们在此报告接受纳昔妥单抗和沙格司亭（GM-CSF）治疗的首次或第二次CR患者的生存情况、毒性和复发模式。
73例连续的HR-NB患者（年龄>18个月时为M期或任何年龄的MYCN扩增的L1/L2期）接受了首次或第二次CR治疗。治疗包括五个周期的皮下（SC）GM-CSF，每天250μg/m²，共5天（第-4至0天），随后是纳昔妥单抗+SC GM-CSF，每天500μg/m²，共5天（第1至5天）。纳昔妥单抗在第1、3和5天以3mg/kg/天的剂量静脉输注30分钟，为门诊治疗。
55例患者处于首次CR，18例处于第二次CR。17例患者患有MYCN扩增的NB，11例在骨髓中可检测到微小残留病。58例（79.5%）患者完成了治疗。4例（5%）出现4级毒性反应，10例（14%）早期复发。三年无事件生存率（EFS）为58.4%，95%置信区间=（43.5%，78.4%），总生存率（OS）为82.4%，95%置信区间=（66.8%，100%）。首次CR患者的三年EFS为74.3%，95%置信区间=（62.7%，88.1%），OS为91.6%，95%置信区间=（82.4%，100%）。首次和第二次CR之间的EFS有显著差异（p = 0.0029）。复发模式主要（75%）为单个器官，主要是骨（54%）。单变量Cox模型显示，既往复发史是EFS的唯一具有统计学意义的预测因素，但不是OS的预测因素。
纳昔妥单抗和GM-CSF巩固治疗使CR期的HR-NB患者生存率极佳。
