Skip to main content
Log in

Immunotherapy for melanoma

Immuntherapie des Melanoms

  • Main Article
  • Published:
Der Onkologe Aims and scope

Abstract

Background

Prior to the approval of the anti-CTLA-4 antibody ipilimumab in 2011, patients suffering from melanoma with distant metastases faced a poor prognosis with a median overall survival of 6–10 months. The approval of immune check point inhibitors, which can achieve long-term survival for patients with metastatic melanoma, represents a breakthrough.

Aim and methods

The currently approved systemic therapies for melanoma, taking into account the data presented at the Annual Meeting 2017 of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), are summarized in this review.

Results and discussion

Compared to ipilimumab, the two anti-PD-1 antibodies pembrolizumab and nivolumab are showing higher efficacy with lower toxicity. The combination of nivolumab and ipilimumab was approved in 2016 and achieved a response rate of 58% and a 3-year survival rate of 58%. Severe grade 3/4 adverse events occurred in 55% of the patients. The early diagnosis of immune-mediated side effects and their adequate treatment, using systemic glucocorticosteroids and other immunosuppressive drugs if necessary, is an indispensable prerequisite for successful therapy. Combined nivolumab and ipilimumab achieved intracranial response rates of 42–55% in patients with metastatic melanoma and brain metastases, with no increase in toxicity compared to patients without brain metastases. In light of the therapeutic success of immune checkpoint inhibitors, several studies are currently underway to evaluate anti-PD-1 antibodies in the adjuvant setting. Current and future studies are increasingly investigating innovative immunocombination therapies, e. g. anti-PD-1 antibodies in combination with IDO inhibitors (IDO, indoleamine-pyrrole 2,3-dioxygenase). Data available now suggest high efficacy and low toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Franklin C, Livingstone E, Roesch A, Schilling B, Schadendorf D (2017) Immunotherapy in melanoma: recent advances and future directions. Eur J Surg Oncol 43(3):604–611

    Article  CAS  Google Scholar 

  2. Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Annu Rev Immunol 22:329–360

    Article  CAS  Google Scholar 

  3. Thompson CB et al (1989) CD28 activation pathway regulates the production of multiple T‑cell-derived lymphokines/cytokines. Proc Natl Acad Sci USA 86(4):1333–1337

    Article  CAS  Google Scholar 

  4. Intlekofer AM, Thompson CB (2013) At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol 94(1):25–39

    Article  CAS  Google Scholar 

  5. Kyi C, Postow MA (2014) Checkpoint blocking antibodies in cancer immunotherapy. Febs Lett 588(2):368–376

    Article  CAS  Google Scholar 

  6. Peggs KS, Quezada SA, Korman AJ, Allison JP (2006) Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol 18(2):206–213

    Article  CAS  Google Scholar 

  7. Hodi FS et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723

    Article  CAS  Google Scholar 

  8. Schadendorf D et al (1894) Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. J Clin Oncol 33(17):1889–2015

    Article  Google Scholar 

  9. Winer A, Bodor JN, Borghaei H (2018) Identifying and managing the adverse effects of immune checkpoint blockade. J Thorac Dis 10:480–S489. https://doi.org/10.21037/jtd.2018.01.111

    Article  Google Scholar 

  10. Robert C et al (2015) Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372(4):320–330

    Article  CAS  Google Scholar 

  11. Hodi FS et al (2016) Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial. Cancer Res 76(14 Supplement):CT1

    Article  Google Scholar 

  12. Hamid O et al (2013) Safety and tumor responses with lambrolizumab (anti-PD-1). N Engl J Med 369(2):134–144

    Article  CAS  Google Scholar 

  13. Robert C et al (2014) Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384(9948):1109–1117

    Article  CAS  Google Scholar 

  14. Daud A et al (2015) Long-term efficacy of pembrolizumab (pembro; MK-3475) in a pooled analysis of 655 patients (pts) with advanced melanoma (MEL) enrolled in KEYNOTE-001. Clin Oncol 33(15_suppl):9005. https://doi.org/10.1200/jco.2015.33.15_suppl.9005

    Article  Google Scholar 

  15. Robert C et al (2015) Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med 372(26):2521–2532

    Article  CAS  Google Scholar 

  16. Robert C et al (2017) Durable complete response after discontinuation of pembrolizumab in patients with metastatic melanoma. J Clin Oncol 36(17):1668–1674. https://doi.org/10.1200/JCO.2017.75.6270

    Article  Google Scholar 

  17. Curran MA, Montalvo W, Yagita H, Allison JP (2010) PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA 107(9):4275–4280

    Article  CAS  Google Scholar 

  18. Wolchok JD et al (2017) Overall survival with combined nivolumab and Ipilimumab in advanced melanoma. N Engl J Med 377(14):1345–1356

    Article  CAS  Google Scholar 

  19. Long GV et al (2017) Standard-dose pembrolizumab in combination with reduced-dose ipilimumab for patients with advanced melanoma (KEYNOTE-029): an open-label, phase 1b trial. Lancet Oncol 18(9):1202–1210

    Article  CAS  Google Scholar 

  20. Tawbi H et al (2017) “Efficacy and safety of nivolumab plus ipilimumab in patients with melanoma metastatic to the brain: results of the phase II study CheckMate 204”. Proc Am Soc Clin Oncol 35:9507

    Article  Google Scholar 

  21. Eggermont AMM et al (1855) Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 375(19):1845

    Article  Google Scholar 

  22. Weber J et al (2017) Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 377(19):1824–1835

    Article  CAS  Google Scholar 

  23. Long GV et al (2017) Adjuvant Dabrafenib plus Trametinib in stage III BRAF-mutated melanoma. N Engl J Med 377(19):1813–1823

    Article  CAS  Google Scholar 

  24. Ascierto PA, McArthur GA (2017) Checkpoint inhibitors in melanoma and early phase development in solid tumors: what’’s the future? J Transl Med 15(1):173

    Article  Google Scholar 

  25. Ribas A (2012) Tumor immunotherapy directed at PD-1. N Engl J Med 366(26):2517–2519

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Frank Friedrich Gellrich.

Ethics declarations

Conflict of interest

F. Meier received fees for consultancy activities and lectures, as well as reimbursement of travel expenses from Roche, Novartis, Bristol-Myers Squibb, and MSD. F.F. Gellrich and S. Beissert declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gellrich, F.F., Beissert, S. & Meier, F. Immunotherapy for melanoma. Onkologe 24 (Suppl 2), 99–103 (2018). https://doi.org/10.1007/s00761-018-0443-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-018-0443-7

Keywords

Navigation