Immune checkpoint inhibitors for the treatment of melanoma

ABSTRACT

Introduction

Immune checkpoint inhibitor (ICI) based immunotherapy is dramatically changing the management of many types of cancers including melanoma. In this malignancy, ICIs prolong disease and progression-free survival as well as overall survival of a percentage of treated patients, becoming the cornerstone of melanoma treatment.

Areas covered

In this review, first, we will describe the mechanisms of immune checkpoint activation and inhibition, second, we will summarize the results obtained with ICIs in melanoma treatment in terms of efficacy as well as toxicity, third, we will discuss the potential mechanisms of immune escape from ICI, and lastly, we will review the potential predictive biomarkers of clinical efficacy of ICI-based immunotherapy in melanoma.

Expert opinion

ICIs represent one of the pillars of melanoma treatment. The success of ICI-based therapy is limited by the development of escape mechanisms, which allow melanoma cells to avoid recognition and destruction by immune cells. These results emphasize the need of additional studies to confirm the efficacy of therapies, which combine different classes of ICIs as well as ICIs with other types of therapies. Furthermore, novel and more effective predictive biomarkers are needed to better stratify melanoma patients in order to define more precisely the therapeutic algorithms.

KEYWORDS:

• CTLA-4
• immune checkpoint inhibitors
• immunotherapy
• irAE
• melanoma
• PD-1
• PD-L1
• predictive biomarkers to immunotherapy

Article highlights

• The ICI-based immunotherapy has dramatically changed the management of metastatic melanoma as well as of complete resected high risk melanoma patients.

• So far, the main drugs used in melanoma treatment are anti-CTLA-4 mAbs and anti-PD-1 mAbs.

• Several ongoing clinical trials are evaluating the role of novel ICIs in melanoma treatment.

• Other trials are currently evaluating ICIs in combination or in different sequencing approaches with other types of therapies.

• A lot of patients do not achieve any benefits from this therapy. Then, the study of immune escape mechanisms is crucial to better understand, while these patients do not respond to ICIs. Moreover, is essential to determine ICI acquired resistance mechanisms.

• In order to define the most correct therapeutic algorithm, it is needed to determine effective predictive biomarkers.

• This box summarizes key points contained in the article.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The author(s) reported that there is no funding associated with the work featured in this article.