Update on immune therapy in melanoma

ABSTRACT

Introduction: Melanoma is the 6th most common cancer in the United States and advanced disease has traditionally been associated with a poor prognosis. Historical therapies had suboptimal activity, including cytotoxic agents and cytokine therapies. However, since 2011, novel targeted therapies and immune checkpoint inhibitors have greatly improved outcomes in this challenging disease.

Areas covered: This article reviews the evolving landscape of advanced melanoma therapeutics, focusing on recent immune therapy advances. We will review clinical data from the last 1-2 years with anti-CTLA-4, anti-PD-1/PDL-1, oncolytic viruses and novel combination approaches. We will discuss landmark clinical trials that led to the integration of these agents into clinical management paradigms. We will also briefly cover the search to identify accurate biomarkers of response to these therapies. Finally, we discuss future directions of clinical research with combination immune therapy strategies.

Expert opinion: Immune checkpoint inhibitors and other immune therapy strategies have redefined melanoma treatment paradigms. A growing number of patients experience durable responses to these agents. Anti-PD-1 directed agents, in particular, provide significant and sustained benefits for a large number of responding patients. Determining the most effective and least toxic combination approaches, and identifying biomarkers of treatment benefit will be key future objectives.

KEYWORDS:

• Melanoma
• immune therapy
• anti-CTLA-4
• anti-PD-1
• anti-PDL-1
• talimogene laherparepvec
• nivolumab
• pembrolizumab
• ipilimumab

Article highlights

• Prior to recent immunotherapy and targeted therapy advances, 5-year survival for advanced melanoma was poor (<10%).

• Checkpoint inhibitors have drastically improved survival with recent data showing a 5-year OS of 34% in patients treated with single-agent nivolumab.

• Combination therapy with ipilimumab and nivolumab has improved efficacy and is considered a current standard of treatment for advanced melanoma.

• Oncolytic immunotherapy agents such as talimogene laherparepvec may be effective especially in those with regional or limited distant metastasis.

• Biomarkers are still needed to predict response with immunotherapy.

• On-going studies will help to determine the optimal combination therapy for advanced melanoma.

This box summarizes key points contained in the article.

Declaration of interest

DB Johnson serves on the advisory boards for Bristol-Myers Squibb and Genoptix. The authors have no other 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.