Abstract
Purpose To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI). Methods Melanoma survivors were identified within two study populations (N = 104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up. Results Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence (N = 8), existential problems (N = 2), survivor guilt (N = 2), and posttraumatic stress disorder (N = 6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity (N = 8), hepatitis (N = 1), colitis (N = 3), and sarcoidosis (N = 1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF. Conclusion A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920.
Highlights
Until 2010, no treatment option had improved overall survival (OS) in patients with metastatic melanoma
Taking into account that survivors included in this study had to be disease-free and without cancer treatment for at least 2 years after initiation of IPI, we considered it appropriate to compare mean scores of our survivor population with the European mean of the healthy population
Fifteen survivors completed the one-year followup assessment (T0): one survivor became ineligible for further assessment due to progression of previously diagnosed prostate cancer, and one survivor had a recurrence of metastatic melanoma
Summary
Until 2010, no treatment option had improved overall survival (OS) in patients with metastatic melanoma. IPI is associated with a range of immune-related adverse events (irAE) such as rash, diarrhea, colitis, hepatitis, hypophysitis, and fatigue occurring both during or even after treatment termination [2] Most of these irAEs are reversible, with the exception of some endocrine and neurological side effects [3]. Given that modulation of immune and endocrine systems 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]
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