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

Journal of Clinical Medicine

Friedegund Meier¹  FrankFriedrich Gellrich¹  Stefan Beissert¹  Marc Schmitz² 

[1] Department of Dermatology, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany;Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany;

关键词: 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;   

DOI  :  10.3390/jcm9010223

来源: DOAJ

【 摘 要 】

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).

【 授权许可】

Unknown