HHE Haematology supplement 2018 - Page 12

A rational approach to select centres to decrease risks and optimise identification of those patients who will benefit most from immunotherapy is required in future References 1 Mora J, Gerald M. The origin of neuroblastic tumors: clues for future therapeutics. Expert Rev Mol Diagn 2004;4(3):293–302. 2 Marshall GM et al. The prenatal origins of cancer. Nat Rev Cancer 2014;14(4):277–89. 3 Ries LAG et al. Cancer incidence and survival among children and adolescents: United States SEER program 1975-1995. Bethesda, MD: National Cancer Institute. 4 Gatta G et al; RARECARE Working Group. Embryonal cancers in Europe. Eur J Cancer 2012;48(10):1425–33. 5 Maris JM. Recent advances in neuroblastoma. N Engl J Med 2010;362:2202–11. 6 Mora J et al. Survival analysis of clinical, pathologic and genetic features in neuroblastoma presenting as local-regional disease. Cancer 2001;91:435–42. 7 Mora J et al. Gerald. Evolving significance of prognostic markers associated with capillary leak syndrome. For all three studies, two treatment-related deaths occurred due to capillary leak syndrome and acute respiratory distress. Toxicities were generally more frequent in patients who received IL-2 compared with patients who did not receive IL-2; in particular, capillary leak syndrome, platelet abnormalities, hypotension, infections, nausea or vomiting, fever, and pain related to ch14.18/CHO.25 In the continuous infusion studies APN311-202 and -303, motor and sensory neuropathies were reported with an incidence of 9% and 5%, respectively. Regarding pain, the authors report that in the continuous infusion studies, around 90% of the patients experienced pain in cycle 1. The percentage of patients with pain decreased in subsequent treatment cycles, to about 60% in cycle 5. The Committee for Medicinal Products for Human Use of the EMA recommended the following indication for dinutuximab beta: treatment of HR neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with history of relapsed or refractory neuroblastoma, with or without residual disease. Before the treatment of relapsed neuroblastoma, any actively progressing disease should be stabilised by other suitable measures. In patients with a history of relapsed/refractory disease and in patients who have not achieved a complete response after first line therapy, dinutuximab beta should be combined with IL-2. These indications are different from those for dinutuximab, which includes only first-line treatment. Dinutuximab beta (Qarziba) is formulated as a concentrate for solution comprising 4.5mg/ml dinutuximab beta formulated with histidine, sucrose, polysorbate 20, hydrochloric acid for adjustment to pH 6.0, and water for injections. To ensure an extractable volume of 4.5ml, the vials are filled with 4.9ml of final product. A solution of 0.9% sodium chloride containing 1% human albumin for dilution is used for the preparation of the final solution for infusion. The recommended posology consists of five new treatment strategies in neuroblastoma. Cancer Lett 2003;197:119–24. 8 Brodeur GM, Bagatell R. Mechanisms of neuroblastoma regression. Nat Rev Clin Oncol 2014;11(12):704-13 9 Cheung NK, Dyer MA. Neuroblastoma: Developmental biology, cancer genomics, and immunotherapy. Nat Rev Cancer 2013;13(6): 397–411. 10 Cheung NK et al. Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Res 1985;45:2642–9. 11 Bosse KR et al. Identification of GPC2 as an oncoprotein and candidate immunotherapeutic target in high-risk neuroblastoma. Cancer Cell 2017;32(3):295–309.e12 12 Hakomori S, Igarashi Y. Functional role of glycosphingolipids in cell recognition and signaling. J Biochem (Tokyo) 1995;118(6):1091–103. 13 Wu Z et al. Expression of GD2 ganglioside by untreated primary human neuroblastomas. Cancer Res 1986;46:440–3. 14 Modak S, Cheung NK. Disialoganglioside directed immunotherapy of neuroblastoma. Cancer Invest 2007;25:67–77. 15 Simon T et al. Consolidation treatment with chimeric anti-GD2 antibody ch14.18 in children older than 1 year with metastatic neuroblastoma. J Clin Oncol 2004;22:3549–57. 16 Cheung NK et al. Monoclonal antibody based therapy of neuroblastoma. Hematol Oncol Clin. North Am 2001;15(5): 853–66. 17 Munn DH, Cheung NK. Antibody-dependent antitumour cytotoxicity by human monocytes cultured with recombinant macrophage colony-stimulating factor. Induction of efficient antibody-mediated antitumour cytotoxicity not detected by 12 HHE 2018 | hospitalhealthcare.com consecutive courses, each course comprising 35 days. 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