METHODS: We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting 123I-Metaiodobenzylguanidine (MIBG) uptake after 4 cycles of immunotherapy were further evaluated by functional Magnetic Resonance Imaging (MRI) and/or Fluorodeoxyglucose (FDG)-positron emission tomography (PET). MIBG avid lesions that became non-restrictive on MRI (apparent diffusion coefficient (ADC) > 1) and/or FDG-PET negative (SUV < 2) were biopsied.
RESULTS: Twenty-seven relapse/refractory (R/R) HR-NB patients were enrolled on protocol Ymabs 201. Two (7.5%) of the 27 showed persistent bone lesions on MIBG, ADC high, and/or FDG-PET negative. Forty-four R/R HR-NB patients received chemo-immunotherapy. Twelve (27%) of the 44 developed persistent MIBG+ but FDG-PET- and/or high ADC lesions. Twelve (86%) of the 14 cases identified were successfully biopsied producing 16 evaluable samples. Histology showed ganglioneuroma maturing subtype in 6 (37.5%); ganglioneuroma mature subtype with no neuroblastic component in 4 (25%); differentiating NB with no Schwannian stroma in 5 (31%); and undifferentiated NB without Schwannian stroma in one (6%). Overall, 10 (62.5%) of the 16 specimens were histopathologically fully mature NBTs.
CONCLUSIONS: Our results disclose an undescribed mechanism of action for naxitamab and highlight the limitations of conventional imaging in the evaluation of anti-GD2 immunotherapy clinical efficacy for HR-NB.
方法:我们报告了接受纳西他单抗治疗化疗难治性NB的患者,显示疾病长期稳定的病变。通过功能磁共振成像(MRI)和/或氟脱氧葡萄糖(FDG)-正电子发射断层扫描(PET)进一步评估了4个周期的免疫治疗后持续摄取123I-甲基碘苄基胍(MIBG)的靶病变。活检在MRI上变得非限制性(表观扩散系数(ADC)>1)和/或FDG-PET阴性(SUV<2)的MIBG狂热病变。
结果:27例复发/难治性(R/R)HR-NB患者纳入方案Ymab201。27人中有2人(7.5%)在MIBG上显示出持续性骨病变,ADC高,和/或FDG-PET阴性。44例R/RHR-NB患者接受化学免疫治疗。44例患者中有12例(27%)出现持续性MIBG+但FDG-PET-和/或高ADC病变。确定的14例病例中有12例(86%)成功进行了活检,产生了16个可评估的样本。组织学显示神经节细胞瘤成熟亚型为6种(37.5%);神经节细胞瘤成熟亚型,无神经母细胞成分4种(25%);分化无Schwannian基质的NB为5(31%);无Schwannian基质的未分化NB为1(6%)。总的来说,16个标本中有10个(62.5%)是组织病理学上完全成熟的NBT。
结论:我们的研究结果揭示了纳他他单抗的作用机制,并强调了常规影像学在评估抗GD2免疫治疗HR-NB临床疗效方面的局限性。