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Coventry BJ, Lilly CA, Hersey P, et al. Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma. J Immunother Cancer. 2014;2:9doi: 10.1186/2051-1426-2-9.
Coventry, B. J., Lilly, C. A., Hersey, P., Michele, A., & Bright, R. J. (2014). Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma. Journal for immunotherapy of cancer, 29. https://doi.org/10.1186/2051-1426-2-9
Coventry, Brendon J, et al. "Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma." Journal for immunotherapy of cancer vol. 2 (2014): 9. doi: https://doi.org/10.1186/2051-1426-2-9
Coventry BJ, Lilly CA, Hersey P, Michele A, Bright RJ. Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma. J Immunother Cancer. 2014 Apr 15;2:9. doi: 10.1186/2051-1426-2-9. eCollection 2014. PMID: 27437102; PMCID: PMC4950896.
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J Immunother Cancer. 2014 Apr 15;2:9. doi: 10.1186/2051-1426-2-9. eCollection 2014.

Prolonged repeated vaccine immuno-chemotherapy induces long-term clinical responses and survival for advanced metastatic melanoma.

Journal for immunotherapy of cancer

Brendon J Coventry, Carrie A Lilly, Peter Hersey, Antonio Michele, Richard J Bright

Affiliations

  1. Discipline of Surgery, University of Adelaide, Adelaide Melanoma Unit, Royal Adelaide Hospital, Adelaide, South Australia Australia.
  2. Kolling Institute University of Sydney, New South Wales, Australia.
  3. Medical Oncology, North Adelaide Oncology, Calvary Hospital, North Adelaide, South Australia 5006 Australia.

PMID: 27437102 PMCID: PMC4950896 DOI: 10.1186/2051-1426-2-9

Abstract

BACKGROUND: Repetitive long-term Vaccinia Melanoma Cell Lysate (VMCL) vaccination schedules have proved clinically effective in producing Complete Responses and strong durable survivals for up to 6.1 years in a previous study of patients with advanced Stage IV and Stage IIIc melanoma. These studies were expanded to include 54 patients for further evaluation of these findings.

METHODS: 54 patients comprising 48 Stage IV (6 M1a, 14 M1b, 28 M1c) and 6 advanced Stage III (5 IIIc; 1 IIIb) were studied using repeated intra-dermal VMCL vaccine therapy. If disease progressed, vaccine was continued together with standard chemotherapy (DTIC and/or Fotemustine). Overall survival was the primary end-point assessed, with clinical responses and toxicity recorded.

RESULTS: From vaccine commencement, median overall survival was 14 months, ranging from 4 to 121 months. Kaplan-Meier survival analysis demonstrated overall 1, 2 and 3-year survival estimates of 57%, 26% and 18.5% respectively, and overall 5-year survival of 15.4%. No appreciable toxicity was observed. Complete Responses (CR) occurred in 16.7% (9) and partial responses (PR) in 14.8% (8) of patients. Stable disease was noted in a further 25 patients (46.3%). No response to therapy was apparent in 12 patients (22.2%). The overall response rate was 31.5% (CR + PR), with clinically significant responses (CR + PR + SD) in 77.8% of patients. Strong, durable clinical responses with overall survivals ≥ 23 months occurred in 29.6% of patients treated with repeated VMCL vaccine for advanced melanoma, (+/- concurrent chemotherapy).

CONCLUSIONS: Prolonged, repetitive VMCL vaccination immunotherapy appears to be a clinically effective means of generating relatively high CR rates, useful clinical responses and long-term survivals, with little toxicity, but remains notably under-explored. Successive immunomodulation might explain the results. Closer analysis of repetitive dosing is required to improve clinical response rates and survival, perhaps by optimising the timing of immunotherapy delivery.

TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ANZCTRN12605000425695.

Keywords: Complete response; Immuno-Chemotherapy; Immunotherapy; Metastatic melanoma; Repetitive vaccinations; Survival; VMCL; Vaccine

References

  1. J Clin Oncol. 2002 Dec 1;20(23):4549-54 - PubMed
  2. Cancer Manag Res. 2012;4:137-49 - PubMed
  3. J Clin Oncol. 2004 Mar 15;22(6):1118-25 - PubMed
  4. Clin Cancer Res. 2013 Oct 1;19(19):5300-9 - PubMed
  5. N Engl J Med. 2012 Jul 12;367 (2):107-14 - PubMed
  6. Cancer Manag Res. 2012;4:215-21 - PubMed
  7. N Engl J Med. 2012 Jun 28;366(26):2443-54 - PubMed
  8. J Transl Med. 2009 Nov 30;7:102 - PubMed
  9. Clin Cancer Res. 2011 Jul 1;17(13):4550-7 - PubMed
  10. Expert Opin Investig Drugs. 2002 Jan;11(1):75-85 - PubMed
  11. World J Surg. 1992 Mar-Apr;16(2):251-60 - PubMed
  12. N Engl J Med. 2010 Aug 26;363(9):809-19 - PubMed
  13. Ann N Y Acad Sci. 2013 Jul;1291:1-13 - PubMed
  14. N Engl J Med. 2010 Aug 19;363(8):711-23 - PubMed
  15. Cancer J. 2011 Sep-Oct;17(5):379-96 - PubMed
  16. N Engl J Med. 2011 Jun 30;364(26):2517-26 - PubMed
  17. J Clin Oncol. 2012 Aug 20;30(24):3012-9 - PubMed
  18. Ann N Y Acad Sci. 1993 Aug 12;690:167-77 - PubMed
  19. N Engl J Med. 2011 Jun 30;364(26):2507-16 - PubMed
  20. Lancet Oncol. 2012 Sep;13(9):849 - PubMed
  21. Clin Cancer Res. 2012 Apr 1;18(7):2039-47 - PubMed
  22. J Clin Oncol. 2008 Feb 1;26(4):527-34 - PubMed
  23. Clin Cancer Res. 2006 Apr 1;12(7 Pt 2):2353s-2358s - PubMed
  24. J Clin Oncol. 2002 Oct 15;20(20):4181-90 - PubMed
  25. J Surg Oncol. 2011 Sep;104(4):420-4 - PubMed
  26. Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4 - PubMed
  27. Ann Surg Oncol. 2012 Aug;19(8):2547-55 - PubMed
  28. Cancer Res. 2003 Aug 1;63(15):4490-6 - PubMed
  29. Melanoma Res. 2003 Jun;13(3):263-9 - PubMed
  30. N Engl J Med. 2012 Jun 28;366(26):2455-65 - PubMed

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