Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes and the Microbiome in Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier

Authors

Margaux Robert
Satabdi Saha
Nazli Dizman
Michelle Rohlfs
Elizabeth Sirmans
Julie Simon
Rodabe N Amaria
Isabella C Glitza Oliva
Hussein A Tawbi
Michael A Davies
Alexandra Ikeguchi
Karen Basen-Engquist
Keri Schadler
Michael E Roth
Wenye Song
Xiaotao Zhang
Nadim J Ajami
Lorenzo Cohen
Jennifer A Wargo
Christine B Peterson
Jennifer L McQuade
Carrie R Daniel

Language

English

Publication Date

12-22-2025

Journal

Nutrients

DOI

10.3390/nu18010040

PMID

41515159

PMCID

PMC12787744

PubMedCentral® Posted Date

12-22-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening questionnaires for depression, anxiety, diet and physical activity. The gut microbiome was characterized via metagenomic sequencing in a subsample (n = 39). Patients' clinicopathological characteristics and experience of irAEs (during treatment) and CT (persisting >6 months after completion of therapy) were extracted retrospectively from the medical record.

Results: In the overall cohort, 60% were experiencing CT, while 16% and 20% reported clinically relevant levels of depression and anxiety symptoms, respectively. We observed significant differences in overall gut microbiome composition between survivors with and without CT (p = 0.02). Consumption of fruit and vegetables was inversely associated with anxiety (ρ = 0.3, p = 0.038). Added sugar consumption was correlated with the severity of experienced symptoms (ρ = 0.4, p = 0.003), with pronounced associations across the spectrum of symptoms, including pain, fatigue and shortness of breath (p < 0.05).

Conclusions: These results suggest that CT is experienced by a substantial proportion of ICB-treated metastatic melanoma survivors. Patients experiencing CT also showed distinct microbiome features. However, additional research in prospective settings is needed to confirm these hypotheses.

Keywords

Humans, Melanoma, Male, Female, Middle Aged, Gastrointestinal Microbiome, Patient Reported Outcome Measures, Cancer Survivors, Diet, Aged, Adult, Immunotherapy, Quality of Life, Immune Checkpoint Inhibitors, Depression, Anxiety, Prospective Studies, Exercise, melanoma survivors, immunotherapy, patient-reported outcomes, diet, microbiome

Published Open-Access

yes

Recommended Citation

Robert, Margaux; Saha, Satabdi; Dizman, Nazli; et al., "Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes and the Microbiome in Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier" (2025). Faculty, Staff and Student Publications. 5516.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5516