131-iodine-metaiodobenzylguanidine (MIBG) as induction therapy
Clinical trials and pilot studies continue to assess the feasibility and tolerability of incorporating MIBG therapy in induction regimens for patients with high-risk neuroblastoma.[103]Weiss BD, Yanik G, Naranjo A, et al. A safety and feasibility trial of (131) I-MIBG in newly diagnosed high-risk neuroblastoma: a Children's Oncology Group study. Pediatr Blood Cancer. 2021 Oct;68(10):e29117.
http://www.ncbi.nlm.nih.gov/pubmed/34028986?tool=bestpractice.com
[104]Mastrangelo S, Attinà G, Zagaria L, et al. Induction regimen in high-risk neuroblastoma: a pilot study of highly effective continuous exposure of tumor cells to radio-chemotherapy sequence for 1 month. The critical role of iodine-131-metaiodobenzylguanidine. Cancers (Basel). 2022 Oct 21;14(20):5170.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9599979
http://www.ncbi.nlm.nih.gov/pubmed/36291955?tool=bestpractice.com
Targeted molecular therapies
These include inhibitors of anaplastic lymphoma kinase (ALK), Wee1 inhibitors, and combined protein tyrosine kinase inhibitor/mTOR inhibition (RIST protocol), among others.[105]Fischer M, Moreno L, Ziegler DS, et al. Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: an open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol. 2021 Dec;22(12):1764-76.
http://www.ncbi.nlm.nih.gov/pubmed/34780709?tool=bestpractice.com
[106]Goldsmith KC, Park JR, Kayser K, et al. Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results. Nat Med. 2023 May;29(5):1092-102.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10202811
http://www.ncbi.nlm.nih.gov/pubmed/37012551?tool=bestpractice.com
[107]Cole KA, Ijaz H, Surrey LF, et al. Pediatric phase 2 trial of a WEE1 inhibitor, adavosertib (AZD1775), and irinotecan for relapsed neuroblastoma, medulloblastoma, and rhabdomyosarcoma. Cancer. 2023 Jul 15;129(14):2245-55.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.34786
http://www.ncbi.nlm.nih.gov/pubmed/37081608?tool=bestpractice.com
[108]Corbacioglu S, Lode H, Ellinger S, et al. Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2024 Jul;25(7):922-32.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00202-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38936379?tool=bestpractice.com
Immunotherapy
Immunological approaches to the treatment of neuroblastoma are being investigated in early-phase trials, including chimeric antigen receptor (CAR) modified T-cell and natural killer T-cell therapies, and monoclonal antibodies targeting the immunomodulatory glycoprotein B7-H3.[109]Louis CU, Savoldo B, Dotti G, et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood. 2011 Dec 1;118(23):6050-6.
http://www.bloodjournal.org/content/118/23/6050.long?sso-checked=true
http://www.ncbi.nlm.nih.gov/pubmed/21984804?tool=bestpractice.com
[110]ClinicalTrials.gov. 131I-burtomab radioimmunotherapy for neuroblastoma central nervous system/leptomeningeal metastases. ClinicalTrials.gov identifier: NCT03275402. Dec 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03275402
[111]ClinicalTrials.gov. Enoblituzumab (MGA271) in children with B7-H3-expressing solid tumors. ClinicalTrials.gov identifier: NCT02982941. Feb 2022 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT02982941
[112]ClinicalTrials.gov. Testing the combination of two immunotherapy drugs (magrolimab and dinutuximab) in patients with relapsed or refractory neuroblastoma or relapsed osteosarcoma. ClinicalTrials.gov identifier: NCT04751383. Mar 2022 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT04751383
[113]ClinicalTrials.gov. C7R-GD2.CART cells for patients with relapsed or refractory neuroblastoma and other GD2 positive cancers (GAIL-N). ClinicalTrials.gov identifier: NCT03635632. Nov 2021 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03635632
[114]ClinicalTrials.gov. GD2 specific CAR and interleukin-15 expressing autologous NKT cells to treat children with neuroblastoma (GINAKIT2). ClinicalTrials.gov identifier: NCT03294954. Jan 2022 [internet publication].
https://clinicaltrials.gov/ct2/show/NCT03294954
Burtomab has been granted breakthrough therapy designation by the US Food and Drug Administration (FDA) for children with relapsed or refractory metastatic neuroblastoma with central nervous system or leptomeningeal metastasis.