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.[102]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
[103]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.[104]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
[105]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
[106]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
[107]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
Immunologic 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.[108]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
[109]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
[110]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
[111]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
[112]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
[113]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 Food and Drug Administration (FDA) for children with relapsed or refractory metastatic neuroblastoma with central nervous system or leptomeningeal metastasis.