Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma

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 measurab...

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Autores: Mora J, Castañeda A, Colombo MC, Gorostegui M, Gomez F, Mañe S, Santa-Maria V, Garraus M, Macias N, Perez-Jaume S, Muñoz O, Muñoz JP, Barber I, Suñol M
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p19366
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19366
Access Level:acceso abierto
Palabra clave:neuroblastoma
anti-GD2 immunotherapy
naxitamab
differentiation
functional MRI
functional imaging
CHD5
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spelling Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk NeuroblastomaMora JCastañeda AColombo MCGorostegui MGomez FMañe SSanta-Maria VGarraus MMacias NPerez-Jaume SMuñoz OMuñoz JPBarber ISuñol Mneuroblastomaanti-GD2 immunotherapynaxitamabdifferentiationfunctional MRIfunctional imagingCHD5Simple 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.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19366CancersISSN: 20726694reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p193662026-05-27T12:37:41Z
dc.title.none.fl_str_mv Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
title Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
spellingShingle Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
Mora J
neuroblastoma
anti-GD2 immunotherapy
naxitamab
differentiation
functional MRI
functional imaging
CHD5
title_short Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
title_full Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
title_fullStr Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
title_full_unstemmed Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
title_sort Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma
dc.creator.none.fl_str_mv Mora J
Castañeda A
Colombo MC
Gorostegui M
Gomez F
Mañe S
Santa-Maria V
Garraus M
Macias N
Perez-Jaume S
Muñoz O
Muñoz JP
Barber I
Suñol M
author Mora J
author_facet Mora J
Castañeda A
Colombo MC
Gorostegui M
Gomez F
Mañe S
Santa-Maria V
Garraus M
Macias N
Perez-Jaume S
Muñoz O
Muñoz JP
Barber I
Suñol M
author_role author
author2 Castañeda A
Colombo MC
Gorostegui M
Gomez F
Mañe S
Santa-Maria V
Garraus M
Macias N
Perez-Jaume S
Muñoz O
Muñoz JP
Barber I
Suñol M
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv neuroblastoma
anti-GD2 immunotherapy
naxitamab
differentiation
functional MRI
functional imaging
CHD5
topic neuroblastoma
anti-GD2 immunotherapy
naxitamab
differentiation
functional MRI
functional imaging
CHD5
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19366
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=19366
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
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