Long-Term Survival, Quality of Life, and Psychosocial Outcomes in Advanced Melanoma Patients Treated with Immune Checkpoint Inhibitors

Abstract

Immune checkpoint inhibitors have become a standard of care option for the treatment of patients with advanced melanoma. Since the approval of the first immune checkpoint (CTLA-4) inhibitor ipilimumab in 2011 and programmed death-1 (PD-1) blocking monoclonal antibodies pembrolizumab and nivolumab thereafter, an increasing proportion of patients with unresectable advanced melanoma achieved long-term overall survival. Little is known about the psychosocial wellbeing, neurocognitive function, and quality of life (QOL) of these survivors. Knowledge about the long term side-effects of these novel treatments is scarce as long-term survivorship is a novel issue in the field of immunotherapy. The purpose of this review is to summarize our current knowledge regarding the survival and safety results of pivotal clinical trials in the field of advanced melanoma and to highlight potential long-term consequences that are likely to impact psychosocial wellbeing, neurocognitive functioning, and QOL. The issues raised substantiate the need for clinical investigation of these issues with the aim of optimizing comprehensive health care for advanced melanoma survivors.

Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab

“…Given that modulation of immune and endocrine systems also impacts on the normal function of the central nervous system (CNS), immune checkpoint blockade has the potential to give rise to neuropsychiatric symptoms such as depressive mood, anxiety, and impairment in neurocognitive function [4]. Despite this potential, little is known about the long-term effects of immune checkpoint inhibitors (ICI) on neuropsychiatric symptoms in individuals with metastatic melanoma [1].…”

Health-related quality of life of long-term advanced melanoma survivors treated with anti-CTLA-4 immune checkpoint inhibition compared to matched controls

“…Although ipilimumab is frequently associated with adverse events, such as dermatological and gastrointestinal toxicities, most of these, except those due to endocrinological immune-related toxicities, are largely reversible [11]. The impact of ipilimumab on HRQoL during the induction phase has only been evaluated in few studies and the results of these studies were not unequivocal [12][13][14][15][16][17][18][19].…”

From Conventional Therapies to Immunotherapy: Melanoma Treatment in Review

“…The tumor responses according to the Response Criteria in Solid Tumors (RECIST) criteria varied from 5.7% to 11.0% in the anti-CTLA-4 treatment arms. The median overall survival (OS) was improved to 10 months for the anti-CTLA-4 monotherapy arm as compared to 6.4 months for the peptide vaccine-alone arm (HR 0.68; p < 0.001 [ 58 ], CA184-002, NCT00094653). The five-year survival rate was 18.2% (95% CI, 13.6% to 23.4%) for patients treated with anti-CTLA-4 + dacarbazine vs. 8.8% (95% CI, 5.7% to 12.8%) for patients treated with placebo plus dacarbazine ( p = 0.002, CA184-024, NCT00324155) [ 59 ].…”

“…Also, the combination of reovirus and radiation has shown to increase the tumor growth delay of the melanoma xenografts in the treated animals, and significantly improve the overall survival rate compared to the treatment with either of the individual therapies [ 118 ]. Importantly, Ras mutation is one of the driver mutations for melanoma and is associated with radio-resistance [ 58 ]. However, some viruses like: reovirus, VSV and HSV have been able to selectively target the Ras mutated melanoma cells and mediate cell death [ 119 ].…”