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Long-Term Outcomes of Immune Checkpoint Inhibition in Metastatic Melanoma

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Abstract

Increasing knowledge about the biology of melanoma and of immunology has led to the development and regulatory approval of the immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab, which are indicated for the treatment of melanoma irrespective of the B-Raf proto-oncogene mutation status of the tumour. Only a subset of patients will respond, but those who do can expect long-lasting, previously unheard-of responses. Long-term survival results for the registration trials, including CheckMate 067, Keynote-006, and Keynote-001, have recently been published. In particular, the combination of ipilimumab and nivolumab showed an impressive 5-year overall survival of just over 50%. However, toxicity remains a significant concern, with some of the side effects being life threatening and/or life changing. In this review, we discuss the safety and efficacy data of all the agents currently approved for the first-line treatment of advanced melanoma, identifying factors that influence the choice of a single agent rather than combination therapy. We highlight the potential biomarkers of response, effects of long-term toxicity, and options after progression.

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  1. Department of Oncology, The University of Oxford, Oxford, OX 37LE, UK

    Francesca Aroldi & Mark R. Middleton

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  1. Francesca Aroldi
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Correspondence to Francesca Aroldi.

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Francesca Aroldi received a travel grant to a congress from Nucana and is currently employed by AstraZeneca. Mark Middleton has received grants from Roche and AstraZeneca; grants and personal fees from GSK; personal fees and other from Novartis, BMS, and BioLineRx; grants, personal fees, and other from Immunocore; other from Pfizer and Regeneron; personal fees, non-financial support, and other from Merck/MSD; personal fees and non-financial support from Replimune; personal fees from Kineta and Silicon Therapeutics; and grants from GRAIL outside the submitted work

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FA made a substantial contribution to the concept and design of the article, literature research, and drafted the article. MM made a substantial contribution to the interpretation of data for the article, and revised it critically for important intellectual content. FA and MM approved the version to be published.

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Aroldi, F., Middleton, M.R. Long-Term Outcomes of Immune Checkpoint Inhibition in Metastatic Melanoma. Am J Clin Dermatol 23, 331–338 (2022). https://doi.org/10.1007/s40257-022-00681-4

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