{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T10:58:16Z","timestamp":1777114696895,"version":"3.51.4"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Naxitamab is an anti-GD2 antibody currently approved in the United States as a treatment option for refractory and\/or relapsed (R\/R) high-risk (HR) neuroblastoma. With the identification of various mutations in tumor tissue by next-generation sequencing, patients with cancer increasingly have access to targeted therapies, including those directed at anaplastic lymphoma kinase (ALK) mutations. Here, we report a 12-year-old patient with refractory HR stage M neuroblastoma according to the International Neuroblastoma Risk Group staging system, with persistent bone and bone marrow involvement for 3 years, who was successfully treated with combined naxitamab and lorlatinib. After an ALK mutation was identified in the primary tumor tissue using the Pillar OncoReveal Multi-Cancer CNV RNA Fusion Panel, lorlatinib was initiated. Naxitamab therapy was subsequently added because of ongoing bone and bone marrow involvement. Our patient achieved complete remission with the combination of naxitamab and lorlatinib according to the International Neuroblastoma Response Criteria. Mild adverse events occurred during the combined immunotherapy, including transient hypotension managed with intravenous fluids and abdominal and leg pain that improved with analgesics. In conclusion, our case showed that combination therapy with naxitamab and lorlatinib may improve long-term outcomes and reduce chemotherapy-related toxicity.<\/jats:p>","DOI":"10.3389\/fonc.2026.1790294","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:20:40Z","timestamp":1774243240000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Concurrent naxitamab and lorlatinib in a patient with refractory high-risk neuroblastoma: a case report"],"prefix":"10.3389","volume":"16","author":[{"given":"Sultan","family":"Aydin","sequence":"first","affiliation":[{"name":"Pediatric Hematology and Oncology, Antalya Training and Research Hospital","place":["Antalya, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse","family":"Oz","sequence":"additional","affiliation":[{"name":"Pediatric Hematology and Oncology, Antalya Training and Research Hospital","place":["Antalya, T\u00fcrkiye"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2017.1285230","article-title":"Overview and recent advances in the treatment of neuroblastoma","volume":"17","author":"Whittle","year":"2017","journal-title":"Expert Rev Anticancer Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2025.101122","article-title":"Global, regional, and national burden of neuroblastoma and other peripheral nervous system tumors, 1990 to 2021 and predictions to 2035: visualizing epidemiological characteristics based on GBD 2021","volume":"60","author":"Yue","year":"2025","journal-title":"Neoplasia"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/biom12030358","article-title":"Anti-GD2 directed immunotherapy for high-risk and metastatic neuroblastoma","volume":"12","author":"Chan","year":"2022","journal-title":"Biomolecules"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa0911123","article-title":"Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma","volume":"363","author":"Yu","year":"2010","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.6011","article-title":"FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor","volume":"24","author":"Cheung","year":"2006","journal-title":"J Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01467-4","article-title":"Naxitamab: first approval","volume":"81","author":"Markham","year":"2021","journal-title":"Drugs"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/2767-9764.crc-24-0338","article-title":"Long-lasting response to lorlatinib in patients with ALK-driven relapsed or refractory neuroblastoma monitored with circulating tumor DNA analysis","volume":"4","author":"Ek","year":"2024","journal-title":"Cancer Res Commun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02297-5","article-title":"Lorlatinib with or without chemotherapy in ALK-driven refractory\/relapsed neuroblastoma: phase 1 trial results","volume":"29","author":"Goldsmith","year":"2023","journal-title":"Nat Med"},{"key":"B9","article-title":"Naxitamab: short chapter","volume-title":"LiverTox: Clinical and Research Information on Drug-Induced Liver Injury","year":"2024"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/jco.21.02478","article-title":"Outcomes following GD2-directed postconsolidation therapy for neuroblastoma after cessation of random assignment on ANBL0032: a report from the Children\u2019s Oncology Group","volume":"40","author":"Desai","year":"2022","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"S833","DOI":"10.1016\/j.annonc.2021.08.1348","article-title":"963MO naxitamab for the treatment of refractory\/relapsed high-risk neuroblastoma (HR NB): updated efficacy and safety data from the international, multicenter phase II trial 201","volume":"32","author":"Mora","year":"2021","journal-title":"Ann Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1520171","article-title":"High-risk neuroblastoma in Mexico: from multimodal treatment to immunotherapy. Regarding the first case treated with naxitamab","volume":"15","author":"Olaya Vargas","year":"2025","journal-title":"Front Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1627","DOI":"10.1002\/cnr2.1627","article-title":"Outpatient administration of naxitamab in combination with granulocyte-macrophage colony-stimulating factor in patients with refractory and\/or relapsed high-risk neuroblastoma: Management of adverse events","volume":"6","author":"Mora","year":"2023","journal-title":"Cancer Rep (Hoboken)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2012.72","article-title":"Targeting ALK in neuroblastoma--preclinical and clinical advancements","volume":"9","author":"Carpenter","year":"2012","journal-title":"Nat Rev Clin Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31845","article-title":"Pulmonary toxicity associated with concurrent lorlatinib and anti-GD2 monoclonal antibody therapy in patients with neuroblastoma","volume":"72","author":"Wei","year":"2025","journal-title":"Pediatr Blood Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1001\/jamaoncol.2018.4005","article-title":"Humanized 3F8 anti-GD2 monoclonal antibody dosing with granulocyte-macrophage colony-stimulating factor in patients with resistant neuroblastoma","volume":"4","author":"Kushner","year":"2018","journal-title":"JAMA Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1790294\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T05:20:41Z","timestamp":1774243241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1790294\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":16,"alternative-id":["10.3389\/fonc.2026.1790294"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1790294","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"article-number":"1790294"}}