The data show more reported grade 3C5 adverse events in patients aged??70?years and a trend towards a higher incidence of irAEs requiring treatment with immune-modulating medication in this group. at a higher risk of immune-related PR-104 adverse events and early treatment discontinuation.Geriatric assessment could help identify older patients that will benefit from immune checkpoint inhibitors. Open in a separate window Introduction In recent years, the number of older patients with cancer is strongly increasing as a result of the ageing of Western societies. In the Netherlands, 45% of patients with melanoma, 68% of patients with lung cancer and 69% of patients with urinary tract cancer are aged older than 65?years . Cancer in older patients frequently appears in the context of comorbid diseases, frailty PGC1A and geriatric problems such as physical or cognitive impairment , which has been shown to affect the ability to endure toxic cancer treatments . Previous studies demonstrated that older patients are at increased risk of chemotherapy toxicity . Additionally, the risk of dying from other causes increases with age [4, 5], which means that some patients may not have the remaining life expectancy to benefit from anti-cancer therapy. Therefore, it is important to weigh the benefits and risks of anti-cancer treatment in older patients. In recent years, immunotherapy targeting checkpoint inhibition has improved the treatment of different types of cancer. Immunological checkpoint molecules suppress the attack of tumour-specific T cells, which usually are an integral part of anti-tumour immunity [6, 7]. Some checkpoint inhibitors block the interaction between programmed cell death-1 (PD-1) on T cells and its ligand PD-L1 on cancer cells and myeloid cells [6, 8]. Others target cytotoxic T-lymphocyte antigen-4 (CTLA-4), which blocks negative signals during T-cell interaction with antigen-presenting cells and depletes regulatory T cells, thereby restoring and enhancing T-cell reactivity [9, 10]. These drugs are used in an expanding group of tumour types but are most PR-104 successful in advanced and metastasized melanoma, where progression-free survival (PFS) and overall survival (OS) have strongly improved [11C14]. However, it is possible that checkpoint inhibitors may be less efficient in older patients because of an ageing immune system (immunosenescence) [6, 7]. The numbers of dendritic PR-104 cells and CD4+? naive T cells decline while the pool of terminally differentiated CD8+?T cells increases [7, 15]. In addition, the number of circulating and intra-tumoural myeloid-derived suppressor cells increases. Hence, T-cell function may decrease and lead to impaired responsiveness to therapies aiming to boost tumour immunity [6, 16]. Treatment with checkpoint inhibitors is expensive, costing around 50,000C80,000 euros per treatment . Because checkpoint inhibitors potentially have serious adverse events and are costly, it is essential to determine which patients truly benefit from therapy and at what risk. The aim of this review is to provide a summary of available efficacy data, to provide an overview of the occurrence of adverse events of checkpoint inhibitors in older patients and to evaluate the available evidence on the treatment of these adverse events. We performed an explorative search on PubMed using the following keywords: Elderly, Older, Immune Checkpoint Inhibitors, Immunotherapy, Toxicity, and Immune-related adverse events. We additionally searched through the references of the publications found and we searched abstracts presented at recent oncology conferences. Treatment Efficacy of Immune Checkpoint Inhibitors in Older Patients Melanoma Several studies have shown the effectiveness of immune checkpoint inhibitors in melanoma for patients of all ages. In 2018, an update of the Cochrane review was performed with respect to systemic treatments for metastatic cutaneous melanoma , which showed that with regard to immune checkpoint inhibitors, anti-PD-1 improved OS compared with chemotherapy, and probably improved PFS. Anti-PD-1 was associated with a better OS and PFS compared with anti-CTLA-4. Anti-CTLA-4 plus chemotherapy probably increased PFS compared with chemotherapy alone, but was not significantly associated with an OS gain. Last, the combination of anti-CTLA-4 plus anti-PD-1, as compared with anti-CTLA-4 alone, was associated with better PFS. Patients in this Cochrane review had a mean age of 57.5?years at the time of treatment randomisation, representing a younger population than general patients with melanoma (Table?1). Table?1 Overview of systemic treatments for metastatic cutaneous melanoma  confidence interval, cytotoxic T-lymphocyte antigen-4, grade 3, hazard ratio, programmed cell death-1, relative risk In the general older.
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