Zusammenfassung
Durch zielgerichtete Behandlungsoptionen und Immuncheckpointinhibitoren wurde die Prognose von Patienten mit metastasiertemMelanom deutlich verbessert. Dennoch bedarf es weiterer Forschungsbestrebungen. Zurzeit stehen zum Beispiel verschiedene Kombinationen von Checkpointinhibitoren untereinander und mit anderen Substanzen im Fokus der Forscher.
Literatur
Garbe C, Leiter U. Melanoma epidemiology and trends. Clin Dermatol. 2009;27(1):3–9.
Leiter U, Garbe C. Epidemiology of melanoma and nonmelanoma skin cancer-the role of sunlight. Adv Exp Med Biol. 2008;624:89–103.
Hölzel D, Engel J. Epidemiologie von malignen Erkrankungen zwischen 20 und 30 Jahren 2011. https://www.onkopedia.com/de/wissensdatenbank/ wissensdatenbank/wissensdatenbank/heranwachsende-und-junge- erwachsene-aya-adolescents-and-young-adults/HoelzelAYA.pdf.
Garbe C et al. Diagnosis and treatment of melanoma: European consensus- based interdisciplinary guideline. Eur J Cancer. 2010;46(2):270–83.
Green AC et al. Population-based 20-year survival among people diagnosed with thin melanomas in Queensland, Australia. J Clin Oncol. 2012;30(13):1462–7.
Davies H et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949–54.
Eigentler TK et al. S3-Leitlinie zur Diagnostik, Therapie und Nachsorge des Melanoms, Version 3.0-April 2018; AWMF-Register-Nummer: 032/024OL; http://www.awmf.org/uploads/tx_szleitlinien/032- 024OL_l_S3_Melanom-Diagnostik-Therapie-Nachsorge_2018-05.pdf
Dummer R et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018; 19(5):603–15.
Gooden MJ et al. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer. 2011;105(1):93–103.
Yazdi AS et al. Heterogeneity of T-cell clones infiltrating primary malignant melanomas. J Invest Dermatol. 2006;126(2):393–8.
Schwartzentruber DJ et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011;364(22):2119–27.
Rosenberg SA et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer. 2008;8(4):299–308.
Thurner B et al. Vaccination with mage-3A1 peptide-pulsed mature, monocyte-derived dendritic cells expands specific cytotoxic T cells and induces regression of some metastases in advanced stage IV melanoma. J Exp Med. 1999;190(11):1669–78.
Garbe C, Eigentler TK. Diagnosis and treatment of cutaneous melanoma: state of the art 2006. Melanoma Res. 2007;17(2):117–27.
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
Stronen E et al. Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. Science. 2016;352(6291):1337–41.
Fong L, Small EJ. Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerging class of immunomodulatory antibodies for cancer treatment. J Clin Oncol. 2008;26(32):5275–83.
Hodi FS et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.
Robert C et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–26.
Topalian SL et al. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24(2):207–12.
Taube JM et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20(19):5064–74.
Ribas A et al. Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. JAMA. 2016;315(15):1600–9.
Ribas A et al. Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): a randomised, controlled, phase 2 trial. Lancet Oncol. 2015;16(8):908–18.
Schachter J et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;390(10105):1853–62.
Robert C et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372(26):2521–32.
Weber JS et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol.2015;16(4):375–84.
Höller C, Nguyen V. Nivolumab beim fortgeschrittenen, nicht-resezierbaren oder metastasierten Melanom. J Med Drug Rev. 2016;6:11–22.
Hodi FS et al. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016;17(11):1558–68.
Dummer R et al. Preliminary findings from part 1 of COMBI-i: A phase III study of anti–PD-1 antibody PDR001 combined with dabrafenib (D) and trametinib (T) in previously untreated patients (pts) with advanced BRAF V600-mutant melanoma. J Clin Oncol. 2018;36(Suppl 5):189.
Larkin J et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(13):1270–1.
Ribas A et al. KEYNOTE-022 update: phase 1 study of first-line pembrolizumab (pembro) plus dabrafenib (D) and trametinib (T) for BRAF-mutant advanced melanoma. Ann Oncol. 2017;28(Suppl 5):Abstr 1216O.
Fountzilas C et al. Review: Oncolytic Virotherapy, updates and future directions. Oncotarget. 2017;8(60):102617–39.
Puzanov I et al. Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. J Clin Oncol. 2016;34(22):2619–26.
Pirard D et al. Interferon alpha as adjuvant postsurgical treatment of melanoma: a meta-analysis. Dermatology. 2004;208(1):43–8.
Bristol Myers Squibb. Phase 3 Study Evaluating the Safety and Efficacy of Adjuvant Opdivo in Resected High-Risk Melanoma Patients Meets Primary Endpoint 2017. https://news.bms.com/press-release/corporatefinancial-news/phase-3-study-evaluating%C2%A0-safetyand-efficacy-adjuvant-opdivo.
Weide B et al. Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab. Clin Cancer Res. 2016;22(22):5487–96.
Eroglu Z, Ribas A. Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy. Ther Adv Med Oncol. 2016;8(1):48–56.
Spranger S et al. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature. 2015;523(7559):231–5.
Restifo NP et al. Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J Natl Cancer Inst. 1996;88(2):100–8.
D’Urso CM et al. Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression. J Clin Invest. 1991;87(1):284–92.
Sucker A et al. Genetic evolution of T-cell resistance in the course of melanoma progression. Clin Cancer Res. 2014;20(24):6593–604.
Koyama S et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.
Author information
Authors and Affiliations
Corresponding author
Additional information
Interessenkonflikt
Die Autoren erklären, dass sie sich bei der Erstellung des Beitrages von keinen wirtschaftlichen Interessen leiten ließen. Dr. med. Katharina Pietschke und Dr. med. Diana Lomberg erklären, dass keine potenziellen Interessenkonflikte vorliegen. PD Dr. med. Thomas Eigentler gibt Vorträge für MSD Sharp & Dohme, Roche, Bristol-Myers Squibb und Medac an, sowie Adboards für MSD Sharp & Dohme, Bristol-Myers Squibb, Roche und Leo. Der Verlag erklärt, dass die inhaltliche Qualität des Beitrags von zwei unabhängigen Gutachtern geprüft wurde. Werbung in dieser Zeitschriftenausgabe hat keinen Bezug zur CME-Fortbildung. Der Verlag garantiert, dass die CME-Fortbildung sowie die CME-Fragen frei sind von werblichen Aussagen und keinerlei Produktempfehlungen enthalten. Dies gilt insbesondere für Präparate, die zur Therapie des dargestellten Krankheitsbildes geeignet sind.
Rights and permissions
About this article
Cite this article
Pietschke, K., Lomberg, D. & Eigentler, T.K. Aktuelle Immuntherapien des malignen Melanoms. Im Focus Onkologie 21, 44–51 (2018). https://doi.org/10.1007/s15015-018-3604-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s15015-018-3604-z