Mora Jaume, Castañeda Alicia, Colombo Maria Cecilia, Gorostegui Maite, Gomez Fernando, Mañe Salvador, Santa-Maria Vicente, Garraus Moira, Macias Napoleon, Perez-Jaume Sara, Muñoz Oscar, Muñoz Juan Pablo, Barber Ignasi, Suñol Mariona
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain.
Radiology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain.
Cancers (Basel). 2021 Mar 12;13(6):1264. doi: 10.3390/cancers13061264.
Neuroblastic tumors (NBTs) originate from a block in the process of differentiation. Histologically, NBTs are classified in neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN). Current therapy for high-risk (HR) NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 monoclonal antibodies (mAbs). Anti-GD2 mAbs induce immunological cytoxicity but also direct cell death.
We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting I-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.
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.
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.
神经母细胞瘤（NBTs）起源于分化过程中的阻滞。组织学上，NBTs分为神经母细胞瘤（NB）、神经节神经母细胞瘤（GNB）和神经节神经瘤（GN）。目前高危（HR）NB的治疗包括化疗、手术、放疗和抗GD2单克隆抗体（mAbs）。抗GD2 mAbs诱导免疫细胞毒性，但也导致直接细胞死亡。
我们报告了接受纳昔妥单抗治疗的化疗难治性NB患者，这些患者显示病灶长期病情稳定。在免疫治疗4个周期后，对持续摄取I-间碘苄胍（MIBG）的靶病灶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）进行进一步评估。对MRI上变得非限制性（表观扩散系数（ADC）>1）和/或FDG-PET阴性（标准化摄取值<2）的MIBG摄取阳性病灶进行活检。
27例复发/难治性（R/R）HR-NB患者入组Ymabs 201方案。27例中有2例（7.5%）MIBG显示持续骨病灶，ADC高，和/或FDG-PET阴性。44例R/R HR-NB患者接受了化学免疫治疗。44例中有12例（27%）出现持续的MIBG阳性但FDG-PET阴性和/或ADC高的病灶。14例确诊病例中有12例（86%）成功活检，获得16份可评估样本。组织学显示，6例（37.5%）为成熟亚型神经节神经瘤；4例（25%）为无神经母细胞成分的成熟亚型神经节神经瘤；5例（31%）为无雪旺氏基质的分化型NB；1例（6%）为无雪旺氏基质的未分化NB。总体而言，16份标本中有10份（62.5%）在组织病理学上为完全成熟的NBTs。
我们的结果揭示了纳昔妥单抗一种未描述的作用机制，并突出了传统成像在评估HR-NB抗GD2免疫治疗临床疗效方面的局限性。
