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Basis of PD1/PD-L1 Therapies
Open AccessReview

Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

1
Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany
2
Skin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases, 01307 Dresden, Germany
3
Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany
4
National Centre for Tumor Diseases, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(1), 223; https://doi.org/10.3390/jcm9010223 (registering DOI)
Received: 21 December 2019 / Revised: 6 January 2020 / Accepted: 7 January 2020 / Published: 14 January 2020
Until recently, distant metastatic melanoma was considered refractory to systemic therapy. A better understanding of the interactions between tumors and the immune system and the mechanisms of regulation of T-cells led to the development of immune checkpoint inhibitors. This review summarizes the current novel data on the treatment of metastatic melanoma with anti-programmed cell death protein 1 (PD-1) antibodies and anti-PD-1-based combination regimens, including clinical trials presented at major conference meetings. Immune checkpoint inhibitors, in particular anti-PD-1 antibodies such as pembrolizumab and nivolumab and the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab can achieve long-term survival for patients with metastatic melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab were also approved for adjuvant treatment of patients with resected metastatic melanoma. Anti-PD-1 antibodies appear to be well tolerated, and toxicity is manageable. Nivolumab combined with ipilimumab achieves a 5 year survival rate of more than 50% but at a cost of high toxicity. Ongoing clinical trials investigate novel immunotherapy combinations and strategies (e.g., Talimogene laherparepvec (T-VEC), Bempegaldesleukin (BEMPEG), incorporation or sequencing of targeted therapy, incorporation or sequencing of radiotherapy), and focus on poor prognosis groups (e.g., high tumor burden/LDH levels, anti-PD-1 refractory melanoma, and brain metastases). View Full-Text
Keywords: melanoma; PD-1; PD-L1; novel combinations; combination therapies; BEMPEG; T-VEC; LAG-3; IDO1; uveal mealnoma; mucosal melanoma; acral melanoma; desmoplastic melanoma; brain metastases; adjuvant therapy; neoadjuvant therapy melanoma; PD-1; PD-L1; novel combinations; combination therapies; BEMPEG; T-VEC; LAG-3; IDO1; uveal mealnoma; mucosal melanoma; acral melanoma; desmoplastic melanoma; brain metastases; adjuvant therapy; neoadjuvant therapy
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Gellrich, F.F.; Schmitz, M.; Beissert, S.; Meier, F. Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update. J. Clin. Med. 2020, 9, 223.

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