Background Adjuvant ICIs are approved for melanoma, but challenges persist regarding irAEs and their long-term impact on quality of life (QOL). Existing data from clinical trials are limited to highly selected populations and predetermined endpoints, failing to capture real-world experiences and symptom variability. The pathogenesis of irAEs and associated symptoms remains poorly understood. This longitudinal prospective study (NCT04990726) aims to investigate irAEs, symptom burden, and immune/genetic biomarkers in adjuvant ICI-treated melanoma patients in real-world settings.
Methods A total of 240 surgically resected stage II/III/IV melanoma patients initiating adjuvant nivolumab/pembrolizumab, without prior systemic therapy or autoimmune diseases will be enrolled. An additional 35 patients undergoing active surveillance will serve as a comparative reference. Assessments and blood collection occur at baseline, months 1, 3, 6, 12, 18, and 24, and at the occurrence of irAEs. Patient-reported outcomes (PROs) are collected using validated questionnaires for QOL, fatigue, depression, and sleep disturbance. Real-time symptom reporting is facilitated through mobile technology. Primary outcomes include clinical characterization of irAEs (incidence, phenotypes, timing, severity) and quantifying symptom burden. Secondary outcomes focus on identifying immune pathways, therapeutic targets, and immune/genetic biomarkers. Bone health is assessed using dual-energy X-ray absorptiometry (DXA) and biomarkers.
Results To date, 47 patients were enrolled (table 1); follow-up ranged from 1–33 months; 30% of patients on adjuvant ICIs experienced ≥ grade 2 irAEs (hepatitis, pneumonitis, arthritis, polymyalgia rheumatica, hypothyroiditis, adrenal insufficiency, immune thrombocytopenic purpura), leading to treatment hold/discontinuation in 21% without treatment-related deaths. Tumor recurrence occurred in 33%. PROs assessment showed i) a significant decline in EORTC QLQ-C30 physical function scale from 3 to 6 months post ICIs (P=0.007), and cognitive functioning scale between 3 and 12 months (P=0.025), ii) significantly worse FACIT fatigue scale between baseline and 1 month (P=0.013) and 3 months (P=0.024), then trended towards less fatigue, iii) no significant differences in depression, anxiety, or stress scales between all timepoints in DASS-21, and iv) trend towards higher levels of sleep impairment in PROMIS score at 1 and 3 months and less impairment at 6 months (P=0.066) but no significant differences in sleep disturbance between all timepoints (P=0.348). Of 11 patients who underwent baseline DXA, 6 completed follow-ups at 12 months and none had osteoporosis. Biomarker analyses are pending.
Conclusions Preliminary findings show 30% experiencing irAEs, leading to treatment modifications but no treatment-related deaths. Fluctuations in physical function, cognitive functioning, fatigue, and sleep are observed, along with preserved bone health. Immune analysis will provide further insights.
Acknowledgements This work receives support from Dr. Noha Abdel-Wahab’s National Institute of Health K01 Award (K01AI163412), the University of Texas MD Anderson Cancer Center Institutional Research Grant, the Division of Internal Medicine Developmental Award, the Bridge funding award, and the Cancer Survivorship Seed fund.
Trial Registration NCT04990726
Ethics Approval The study obtained ethics approval from the institutional review board at the University of Texas MD Anderson Cancer Center (Protocol 2019–0390). All participants gave informed consent before taking part of this study.
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