Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
Por:
Mora J, Castañeda-Heredia A, Colombo MC, Gorostegui M, Fernando Gómez Muñoz, Mañe S, Santa-María López V, Garraus-Oneca M, Macias N, Pérez-Jaume S, Muñoz-Aznar O, Muñoz JP, Barber-Martínez de la Torre I and Suñol M
Publicada:
1 mar 2021
Ahead of Print:
12 mar 2021
Resumen:
Simple Summary
The anti-tumor activity of anti-GD2 monoclonal antibodies (mAbs) have been demonstrated by the capacity to mediate immunological cytotoxicity but also through direct cell death induction. Recently, studies with anti-GD2 mAbs for high-risk (HR)-neuroblastoma (NB) patients with measurable disease, with or without chemotherapy, have reported significant objective responses. In this subgroup of patients, we observed that, while being treated with the mAb naxitamab, some chemorefractory lesions showed long periods of stable disease. Here, we report a comprehensive imaging evaluation of those lesions correlating with histopathological demonstration of naxitamab-induced tissue differentiation. Our results suggest an undescribed mechanism of action for anti-GD2 mAbs.
Background: 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. Methods: We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting I-123-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.
Filiaciones:
Mora J:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Castañeda-Heredia A:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Colombo MC:
Radiology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Gorostegui M:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Fernando Gómez Muñoz:
Interventional Radiology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
:
Nuclear Medicine Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Santa-María López V:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Garraus-Oneca M:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Macias N:
Interventional Radiology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Pérez-Jaume S:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Muñoz-Aznar O:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Muñoz JP:
Oncology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Barber-Martínez de la Torre I:
Radiology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
Suñol M:
Pathology Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu, 08950 Barcelona, Spain
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