{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:15:18Z","timestamp":1788498918257,"version":"build-2803163510"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017559","name":"Recordati Rare Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017559","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To assess comparative evidence on the independent contribution of GM-CSF to the efficacy and safety of anti-GD2 immunotherapy in neuroblastoma and to identify evidence gaps.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This systematic review was conducted in accordance with the PRISMA guidelines in February 2026. MEDLINE (via PubMed), EMBASE, and the Cochrane Library were searched to identify comparative studies evaluating anti-GD2 immunotherapy with and without GM-CSF in patients with neuroblastoma. In addition, the websites of key oncology societies were searched.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No study directly compared otherwise equivalent anti-GD2 regimens that differed only in the inclusion of GM-CSF. Two studies met the broader comparative eligibility criterion and provided only indirect regimen-level information. Both evaluated older, non-licensed murine anti-GD2 antibodies (m3F8 and 14.G2a), and neither evaluated GM-CSF with currently licensed anti-GD2 antibodies. In the retrospective study by Cheung et\u00a0al., survival outcomes differed across treatment eras; however, GM-CSF was co-administered with 13-cis-retinoic acid and treatment groups also differed with respect to prior stem cell transplantation, induction therapy, baseline characteristics, follow-up duration and supportive care. Therefore, the observed survival differences cannot be attributed to GM-CSF. Toxicity comparisons in this study were also limited by differences in toxicity ascertainment across treatment eras. The prospective phase I\/Ib study by Frost et\u00a0al. was primarily designed to evaluate dose finding and toxicity, included very small and heterogeneous treatment groups, and did not isolate GM-CSF as an independent treatment variable. No eligible comparative study was identified for dinutuximab, dinutuximab beta or naxitamab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Available comparative evidence is insufficient to determine the independent contribution of GM-CSF to the efficacy or safety of anti-GD2 immunotherapy in neuroblastoma. These findings should not be used to justify modification of licensed product-specific anti-GD2 regimens. A randomized trial holding the anti-GD2 backbone and relevant co-interventions constant is needed to isolate the effect of GM-CSF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                      , identifier CRD420251116911.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1932343","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:24:32Z","timestamp":1788495872000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative evidence on the independent contribution of granulocyte-macrophage colony-stimulating factor to anti-GD2 immunotherapy in neuroblastoma: a systematic review and gap analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Aleksandra","family":"Wieczorek","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology and Haematology, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Mielecka-Jarmocik","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology and Haematology, Institute of Pediatrics, Faculty of Medicine, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Synakiewicz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk","place":["Gdansk, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"\u015aladowska","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Drug Research, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Kawalec","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Drug Research, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College","place":["Krakow, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger N.","family":"Lode","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, University Medicine Greifswald","place":["Greifswald, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/BTT.S114530","article-title":"Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy","volume":"13","author":"Keyel","year":"2019","journal-title":"Biologics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31831","article-title":"Accelerating drug development for neuroblastoma: Consensus statement from the third neuroblastoma drug development strategy forum","volume":"72","author":"DuBois","year":"2025","journal-title":"Pediatr Blood Cancer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1080\/14737140.2017.1364995","article-title":"Anti-GD2 immunotherapy for neuroblastoma","volume":"17","author":"Sait","year":"2017","journal-title":"Expert Rev Anticancer Ther"},{"key":"B4","unstructured":"Neuroblastoma"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13164765","article-title":"High-risk neuroblastoma challenges and opportunities for antibody-based cellular immunotherapy","volume":"13","author":"Persaud","year":"2024","journal-title":"J Clin Med"},{"key":"B6","unstructured":"Treating Neuroblastoma"},{"key":"B7","unstructured":"High-Risk Neuroblastoma Standard Clinical Practice Recommendation. 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