Overall survival after relapse in high-risk neuroblastoma: an adjusted indirect comparison of post-relapse dinutuximab beta, historical controls, and relapse after first-line dinutuximab beta maintenance.
17 affiliations
- 1Department of Pediatric Hematology and Oncology, University Medicine Greifswald, Greifswald, Germany.
- 2Department of Nutrition and Drug Research, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Krakow, Poland.
- 3Paediatric Haematology Oncology, Jagiellonian University Medical College, Krakow, Poland.
- 4Children and Adolescent Oncology Department, Gustave Roussy, Paris-Sud University, Paris, France.
- 5Oncology Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Istituto Giannina Gaslini, Genoa, Italy.
- 6Hospital Universitario y Politecnico La Fe, Valencia, Spain.
- 7University College London (UCL) Great Ormond Street Institute of Child Health, London, United Kingdom.
- 8Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine Tel Aviv University, Petach Tikva, Israel.
- 9Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
- 10Division of Pediatric Hematology & Oncology, Vall d'Hebron Barcelona Hospital, Barcelona, Spain.
- 11Centre for Cancer Immunology, University of Southampton, Southampton, United Kingdom.
- 12Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
- 13Department of Pediatric Hematology/Oncology and Stem Cell Transplantation University Hospital Ghent, Ghent, Belgium.
- 14Department of Haematology and Oncology, Children's Health Ireland, Dublin, Ireland.
- 15Centrum HTA Sp. z o.o., Kraków, Poland.
- 16Department of Paediatrics, Saint Anna Children's Hospital, Medical University, Vienna, Austria.
- 17Department of Pediatrics, Medical University Vienna, Vienna, Italy.
Abstract
Objective
To compare overall survival (OS) in patients with relapsed neuroblastoma treated with dinutuximab beta (DB) after relapse with that of two comparator populations: historical controls with no prior anti-disialoganglioside-2 exposure and patients who relapsed after first-line DB maintenance immunotherapy. The objectives were to evaluate the effectiveness of DB in the relapsed setting and to assess a potential legacy effect of prior first-line therapy.Methods
This unanchored indirect comparison used individual patient data from three cohorts: historical controls with no prior anti-GD2 therapy (N/N), patients who relapsed after first-line DB maintenance immunotherapy and did not receive subsequent DB (DB/N), and patients treated with DB after relapse without prior exposure (N/DB). Harmonized eligibility criteria were applied across cohorts, and follow-up was aligned using a common post-relapse index date. Adjusted comparisons were performed using propensity score reweighting. Overall survival was measured from the observed (N/DB) or imputed (N/N and DB/N) post-relapse index date and analyzed using weighted Kaplan-Meier methods and weighted Cox proportional hazards models, with hazard ratios (HR) reported. For the N/N and DB/N cohorts, the post-relapse index date was imputed using a quantile regression model estimating the interval from first relapse to initiation of DB, fitted to data from the N/DB cohort.Results
A total of 329 patients were assessed, of whom 266 were included in the weighted analyses. Baseline imbalances in age at relapse, time from diagnosis, MYCN status, and International Neuroblastoma Staging System (INSS) stage were largely resolved after weighting. No evidence of a legacy effect of first-line DB exposure was observed, as OS did not differ significantly between patients who relapsed after first-line DB maintenance immunotherapy and historical controls (HR = 1.26, 95% CI 0.70-2.26; p=0.437). In contrast, DB administered after relapse was associated with significantly improved OS compared with both historical controls (HR = 0.53, 95% CI 0.35-0.81; p=0.003) and patients who relapsed after first-line DB maintenance immunotherapy (HR = 0.42, 95% CI 0.25-0.72; p=0.001). These findings were consistent across sensitivity analyses.Conclusion and limitations
This adjusted indirect comparison demonstrated that DB administered after relapse was associated with significantly improved OS compared with both historical controls and patients who relapsed after prior first-line DB maintenance immunotherapy. No evidence of a legacy effect of first-line DB immunotherapy was identified. These findings support the clinical relevance of DB in the relapsed setting and indicate that prior first-line DB maintenance alone was not associated with a persistent post-relapse survival advantage. The study did not evaluate DB retreatment after prior first-line exposure.
Related
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BibTeX
@article{lode2026overall,
title = {{Overall survival after relapse in high-risk neuroblastoma: an adjusted indirect comparison of post-relapse dinutuximab beta, historical controls, and relapse after first-line dinutuximab beta maintenance.}},
author = {Holger N Lode and Przemysław Holko and Aleksandra Wieczorek and Katarzyna Śladowska and Nikolai Siebert and Dominique Valteau-Couanet and Alberto Garaventa and Adela Cañete and John Anderson and Isaac Yaniv and Shifra Ash and Lucas Moreno and Juliet Gray and Roberto Luksch and Genevieve Laureys and Cormac Owens and Carla Manzitti and Sascha Troschke-Meurer and Paweł Kawalec and Ruth L Ladenstein},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1933438},
url = {https://europepmc.org/article/MED/42908775},
note = {CC BY},
}
RIS
TY - JOUR
TI - Overall survival after relapse in high-risk neuroblastoma: an adjusted indirect comparison of post-relapse dinutuximab beta, historical controls, and relapse after first-line dinutuximab beta maintenance.
AU - Holger N Lode
AU - Przemysław Holko
AU - Aleksandra Wieczorek
AU - Katarzyna Śladowska
AU - Nikolai Siebert
AU - Dominique Valteau-Couanet
AU - Alberto Garaventa
AU - Adela Cañete
AU - John Anderson
AU - Isaac Yaniv
AU - Shifra Ash
AU - Lucas Moreno
AU - Juliet Gray
AU - Roberto Luksch
AU - Genevieve Laureys
AU - Cormac Owens
AU - Carla Manzitti
AU - Sascha Troschke-Meurer
AU - Paweł Kawalec
AU - Ruth L Ladenstein
PY - 2026
DA - 2026/10/07
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1933438
UR - https://europepmc.org/article/MED/42908775
AB - Objective To compare overall survival (OS) in patients with relapsed neuroblastoma treated with dinutuximab beta (DB) after relapse with that of two comparator populations: historical controls with no prior anti-disialoganglioside-2 exposure and patients who relapsed after first-line DB maintenance immunotherapy. The objectives were to evaluate the effectiveness of DB in the relapsed setting and to assess a potential legacy effect of prior first-line therapy.Methods This unanchored indirect comparison used individual patient data from three cohorts: historical controls with no prior anti-GD2 therapy (N/N), patients who relapsed after first-line DB maintenance immunotherapy and did not receive subsequent DB (DB/N), and patients treated with DB after relapse without prior exposure (N/DB). Harmonized eligibility criteria were applied across cohorts, and follow-up was aligned using a common post-relapse index date. Adjusted comparisons were performed using propensity score reweighting. Overall survival was measured from the observed (N/DB) or imputed (N/N and DB/N) post-relapse index date and analyzed using weighted Kaplan-Meier methods and weighted Cox proportional hazards models, with hazard ratios (HR) reported. For the N/N and DB/N cohorts, the post-relapse index date was imputed using a quantile regression model estimating the interval from first relapse to initiation of DB, fitted to data from the N/DB cohort.Results A total of 329 patients were assessed, of whom 266 were included in the weighted analyses. Baseline imbalances in age at relapse, time from diagnosis, MYCN status, and International Neuroblastoma Staging System (INSS) stage were largely resolved after weighting. No evidence of a legacy effect of first-line DB exposure was observed, as OS did not differ significantly between patients who relapsed after first-line DB maintenance immunotherapy and historical controls (HR = 1.26, 95% CI 0.70-2.26; p=0.437). In contrast, DB administered after relapse was associated with significantly improved OS compared with both historical controls (HR = 0.53, 95% CI 0.35-0.81; p=0.003) and patients who relapsed after first-line DB maintenance immunotherapy (HR = 0.42, 95% CI 0.25-0.72; p=0.001). These findings were consistent across sensitivity analyses.Conclusion and limitations This adjusted indirect comparison demonstrated that DB administered after relapse was associated with significantly improved OS compared with both historical controls and patients who relapsed after prior first-line DB maintenance immunotherapy. No evidence of a legacy effect of first-line DB immunotherapy was identified. These findings support the clinical relevance of DB in the relapsed setting and indicate that prior first-line DB maintenance alone was not associated with a persistent post-relapse survival advantage. The study did not evaluate DB retreatment after prior first-line exposure.
SN - 2234-943X
ER -