#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Implementation of immunotherapy into the treatment of neuroblastoma – single center experience with the administration of dinutuximab and management of its adverse effects


Authors: MUDr. Achbergerová Monika 1;  MUDr. Hederová Stanislava 2;  MUDr. Mikesková Martina 2;  MUDr. Husáková Kristína 2;  MUDr. Hrašková Andrea 1;  doc. MUDr. Kolenová Alexandra, Ph.D. 2
Authors‘ workplace: Klinika detskej hematológie a onkológie NÚDCH, Bratislava, Slovenská republika 1;  Detská onkologická klinika LF UK a DFNsP, Bratislava, Slovenská republika 2
Published in: Klin Onkol 2020; 33(5): 372-378
Category: Original Articles
doi: https://doi.org/10.14735/amko2020372

Overview

Background: Neuroblastoma is the most common extracranial solid tumour of childhood with extremely heterogeneous bio­logical and clinical behaviour. Despite advances in its treatment, the long-term prognosis of patients with a high-risk and relapsed neuroblastoma remains poor. The implementation of immunotherapy into the treatment protocols has the potential to improve it. Dinutuximab, a chimeric monoclonal antibody, leads to the apoptosis of tumour cells through binding to the GD2 receptor. The article aim is to present the first experience of our centre with dinutuximab treatment.

Patients and methods: In 2018–2019, we administered 31 cycles of dinutuximab to seven patients. Five patients with high-risk neuroblastoma received dinutuximab in the first line, in two patients with relapse, dinutuximab was administered in the second line of treatment. To evaluate the toxicity of the treatment, the nursing records of patients during immunotherapy were retrospectively analysed.

Results: Two patients treated with dinutuximab in the first line are in complete remission, three patients achieved a partial response. Both patients with relapsed neuroblastoma were dia­gnosed with a second relapse after immunotherapy and died of disease progression. The treatment tolerance was acceptable in most patients – in six patients adverse events were managed with adequate supportive care. These were mainly symptoms of capillary leak syndrome, pain and hypersensitivity reactions. In one patient, the treatment was discontinued due to severe neurotoxicity.

Conclusion: Dinutuximab has a proven benefit in the eradication of the minimal residual disease in the treatment of neuroblastoma. Immunotherapy is currently the standard for first-line treatment of high-risk neuroblastoma. Its role in the treatment of relapsed neuroblastoma is a subject of several ongoing studies as well as the optimization of therapeutic regimens. Dinutuximab administration is associated with a considerable risk of severe adverse reactions, so the treatment belongs to the hands of an experienced paediatric oncology centre.

Keywords:

dinutuximab – anti-GD2 – monoclonal antibody – neuroblastoma – residual disease


Sources

1. Whittle SB, Smith W, Doherty E et al. Overview and recent advances in the treatment of neuroblastoma. Expert Rev Anticancer Ther 2017; 17 (4): 369–386. doi: 10.1080/14737140.2017.1285230.

2. Sharma R, Mer J, Lion A et al. Clinical presentation, evaluation, and management of neuroblastoma. Pediatr Rev 2018; 39 (4): 194–203. doi: 10.1542/pir.2017-0087.

3. McGinty L, Kolesar J. Dinutuximab for maintenance therapy in pediatric neuroblastoma. Am J Health Syst Pharm 2017; 74 (8): 563–567. doi: 10.2146/ajhp160228.

4. London WB, Boni L, Simon T et al. The role of age in neuroblastoma risk stratification: the German, Italian, and children‘s oncology group perspectives. Cancer Lett 2005; 228 (1–2): 257–266. doi: 10.1016/j.canlet.2004.12.054.

5. Cohn SL, Pearson AD, London WB et al. The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report. J Clin Oncol 2008; 27 (2): 289–297. doi: 10.1200/JCO.2008.16.6785.

6. International Study Protocol: European Low and Intermediate Risk Neuroblastoma Protocol: A SIOPEN Study Version 3.0. [online]. Available from: https: //clinicaltrials.gov/ct2/show/NCT01728155.

7. International Study Protocol: High Risk Neuroblastoma Study 1.5 of SIOP-Europe (SIOPEN). [online]. Available from: https: //www.gyermekdaganat.hu/wp-content/uploads/NBL_01_HRNBL1-7-Protocol-R4-randomisation-Juni-2014.pdf.

8. Mora J. Dinutuximab for the treatment of pediatric patients with high risk neuroblastoma. Expert Rev Clin Pharmacol 2016; 9 (5): 647–653. doi: 10.1586/17512433.2016.1160775.

9. Parsons K, Bernhardt, B, Strickland B. Targeted immunotherapy for high-risk neuroblastoma – the role of monoclonal antibodies. Ann Pharmacother 2013; 47 (2): 210–218. doi: 10.1345/aph.1R353.

10. Yu AL, Gilman AL, Ozkaynak MF et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med 2010; 363 (14): 1324–1334. doi: 10.1056/NEJMoa0911123.

11. Cheung NK, Dyer MA. Neuroblastoma: developmental bio­logy, cancer genomics and immunotherapy. Nat Rev Cancer 2013; 13 (6): 397–411. doi: 10.1038/nrc3526.

12. Matthay KK, Maris JM, Schleiermacher G et al. Neuroblastoma. Nat Rev Dis Primers 2016; 2: 16078.

13. Cook MN, Olshan AF, Guess HA et al. Maternal medication use and neuroblastoma in offspring. Am J Epidemiol 2004; 159 (8): 721–731. doi: 10.1093/aje/kwh108.

14. Menegaux F, Olshan AF, Neglia JP et al. Day care, childhood infections, and risk of neuroblastoma. Am J Epidemiol 2004; 159 (9): 843–851. doi: 10.1093/aje/kwh111.

15. McDermott S, Salzberg DC, Anderson AP et al. Systematic Review of chromium and nickel exposure during pregnancy and impact on child outcomes. J Toxicol Environ Health A 2015; 78 (21–22): 1348–1368. doi: 10.1080/15287394.2015.1090939.

16. Shojaei-Brosseau T, Chompret A, Abel A et al. Genetic epidemiology of neuroblastoma: a study of 426 cases at the Institut Gustave-Roussy in France. Pediatr Blood Cancer 2004; 42 (1): 99–105. doi: 10.1002/pbc.10381.

17. Papaioannou G, McHugh K. Neuroblastoma in childhood: review and radiological findings. Cancer Imaging 2005; 5: 116–127. doi: 10.1102/1470-7330.2005.0104.

18. Berthold F, Boos J, Burdach S et al. Myeloablative megatherapy with autologous stem-cell rescue versus oral maintenance chemotherapy as consolidation treatment in patients with high-risk neuroblastoma: a randomised controlled trial. Lancet Oncol 2005; 6 (9): 649–658. doi: 10.1016/S1470-2045 (05) 70291-6.

19. Park JR, Eggert A, Caron H. Neuroblastoma: bio­logy, prognosis, and treatment. Hematol Oncol Clin North Am 2010; 24 (1): 65–86. doi: 10.1016/j.hoc.2009.11.011.

20. Wu ZL, Schawrtz E, Seeger R et al. Expression of GD2 ganglioside by untreated primary human neuroblastomas. Cancer Res 1986; 46 (1): 440–443.

21. Cheung NK, Saarinen U, Neely JE et al. Development of neuroblastoma monoclonal antibodies for potential utilization in dia­gnosis and therapy. Prog Clin Biol Res 1985; 175: 501–505.

22. Cheung NK, Saarinen U, Neely JE et al. Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells. Cancer Res 1985; 45 (6): 2642–2649.

23. Hoy SM. Dinutuximab: A review in high-risk neuroblastoma. Target Oncol 2016; 11 (2): 247–253. doi: 10.1007/s11523-016-0420-2.

24. Barker E, Mueller BM, Handgretinger R et at. Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res 1991; 51 (1): 144–149.

25. SPC EMA: Unituxin 3.5 mg/mL concentrate for solution for infusion. EU Summary of product characteristics. [online]. Available from: https: //www.ema.europa.eu/en/.

26. Ladenstein R, Potschger U, Valteau-Couanet D et al. Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): a multicentre, randomised, phase 3 trial. Lancet Oncol 2018; 19 (12): 1617–1629. doi: 10.1016/S1470-2045 (18) 30578-3.

27. Matthay KK. Interleukin 2 plus anti-GD2 immunotherapy: helpful or harmful? Lancet Oncol 2018; 19 (12): 1549–1551. doi: 10.1016/S1470-2045 (18) 30627-2.

28. London WB, Castel V, Monclair TW et al. Clinical and bio­logic features predictive of survival after relapse of neuroblastoma: a report from the International Neuroblastoma Risk Group project. J Clin Oncol 2011; 29 (24): 3286–3292. doi: 10.1200/JCO.2010.34.3392.

29. Lau L, Tai D, Weitzman S et al. Factors influencing survival in children with recurrent neuroblastoma. J Pediatr Hematol Oncol 2004; 26 (4): 227–232. doi: 10.1097/00043426-200404000-00003.

30. Garaventa A, Parodi S, De Bernardi B et al. Outcome of children with neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry. Eur J Cancer 2009; 45 (16): 2835–2842. doi: 10.1016/j.ejca.2009.06.010.

31. Mody R, Naranjo A, Van Ryn C et al. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol 2018; 18 (7): 946–957. doi: 10.1016/S1470-2045 (17) 30355-8.

32. Bartholomew J, Washington T, Bergeron S et al. Dinutuximab: A novel immunotherapy in the treatment of pediatric patients with high-risk neuroblastoma. J Pediatr Oncol Nurs 2017; 34 (1): 5–12. doi: 10.1177/ 1043454216659448.

33. Greenwood KL, Foster JH. The safety of dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma. Expert Opin Drug Saf 2018; 17 (12): 1257–1262. doi: 10.1080/14740338.2018.1549221.

34. Keyel ME, Reynolds CP. Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy. Biologics 2019; 13: 1–12. doi: 10.2147/BTT.S114530.

Labels
Paediatric clinical oncology Surgery Clinical oncology

Article was published in

Clinical Oncology

Issue 5

2020 Issue 5

Most read in this issue
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#