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Abstract B055: Disease control in patients treated with naxitamab for refractory/relapsed high-risk neuroblastoma

2024· article· en· W4402266829 on OpenAlexaffabout
Jaume Mora, Godfrey Chi Fung Chan, Daniel A. Morgenstern, Loredana Amoroso, Karsten Nysom, Joerg Faber, Arthur Wingerter, Melissa Bear, Alba Rubio‐San‐Simón, Karen Tornøe, Sharif Koep, Maria Düring, Brian H. Kushner

Bibliographic record

VenueCancer Research · 2024
Typearticle
Languageen
FieldMedicine
TopicNeuroblastoma Research and Treatments
Canadian institutionsHospital for Sick Children
Fundersnot available
KeywordsRefractory (planetary science)MedicineNeuroblastomaDiseaseInternal medicineOncologyBiology

Abstract

fetched live from OpenAlex

Abstract Background: High-risk neuroblastoma (HR-NB) is the most common extracranial solid tumor in children, frequently characterized by residual disease following induction therapy and by relapses. Traditional efficacy measures include complete response (CR) or partial response (PR), both associated with reductions in all disease compartments. Historically poor outcomes and variable treatment responses, particularly among patients with refractory and relapsed disease, underscore the need for insights into the disease control rate (DCR), a composite measure of nonprogression comprising overall response of CR, PR, minor response, and stable disease (SD). Naxitamab is an anti-GD2 humanized monoclonal antibody with established efficacy in patients with refractory/relapsed (R/R) HR-NB in bone and/or bone marrow (BM). In this post hoc analysis, we report the DCR with a 12-week minimum of SD calculated from start of naxitamab treatment, based on data from a prespecified interim analysis of Trial 201. Methods: Ongoing Trial 201 (phase 2, NCT03363373) evaluates naxitamab plus granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with R/R HR-NB with residual disease in bone/BM only. Patients with soft tissue or actively progressing disease were excluded. Naxitamab was infused at 3mg/kg/dose intravenously on Days 1/3/5 with GM-CSF administered subcutaneously on Days -4 to 5 (monthly cycles). Response was evaluated by independent central review using the 2017 International Neuroblastoma Response Criteria. Results: DCR in the overall efficacy population (N=52) was 63% (95% CI, 49%-76%). Patients with an incomplete response in bone and/or BM following induction therapy (refractory disease, n=26) or relapse therapy (relapsed disease, n=26) achieved DCR (95% CI) of 73% (52%-88%) and 54% (33%-73%), respectively. DCR (95% CI) for additional patient subgroups were as follows: with bone disease only at baseline (n=29), 59% (39%-76%); with both bone and BM disease at baseline (n=21), 71% (48%-89%); baseline Curie score (CS) of ≤2 (n=22), 68% (45%-86%); baseline CS ≥3 (n=30), 60% (41%-77%); with prior anti-GD2 therapy (n=13), 46% (19%-75%); and without prior anti-GD2 therapy (n=39), 69% (52%-83%). Conclusions: Patients with R/R HR-NB and residual disease in bone and/or BM treated with naxitamab+GM-CSF achieved a DCR of 63%, providing an important measure for patients at risk for disease progression. Disease control appeared consistent irrespective of baseline CS. While additional studies are needed, the observed trend toward better DCR in those without prior anti-GD2 therapy vs those with prior anti-GD2 therapy may partly reflect the predominance of patients with relapsed disease (12/13) in the latter subgroup. Citation Format: Jaume Mora, Godfrey C. Chan, Daniel A. Morgenstern, Loredana Amoroso, Karsten Nysom, Joerg Faber, Arthur Wingerter, Melissa Bear, Alba Rubio-San-Simon, Karen Tornøe, Sharif Koep, Maria Düring, Brian H. Kushner. Disease control in patients treated with naxitamab for refractory/relapsed high-risk neuroblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B055.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.026
GPT teacher head0.352
Teacher spread0.326 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2024
Admission routes2
Has abstractyes

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