Gut Microbiome

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

TL;DR

Chronic toxicity is experienced by a substantial proportion of ICB-treated metastatic melanoma survivors, and patients experiencing CT showed distinct microbiome features, while dietary factors including fruit/vegetable and added sugar consumption were associated with anxiety and symptom severity.

Key Findings

Sixty percent of long-term ICB-treated metastatic melanoma survivors were experiencing chronic toxicity persisting more than 6 months after completion of therapy.

  • Cohort included 48 patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment.
  • Patients were prospectively enrolled from a melanoma survivorship clinic.
  • Chronic toxicity was defined as persisting >6 months after completion of therapy.
  • Clinicopathological characteristics and experience of irAEs and CT were extracted retrospectively from the medical record.

Clinically relevant levels of depression and anxiety symptoms were reported by 16% and 20% of survivors, respectively.

  • Participants completed screening questionnaires for depression and anxiety.
  • 16% of the overall cohort reported clinically relevant levels of depression symptoms.
  • 20% of the overall cohort reported clinically relevant levels of anxiety symptoms.
  • These mental health assessments were conducted in a cohort of 48 long-term ICB-treated melanoma survivors.

Significant differences in overall gut microbiome composition were observed between survivors with and without chronic toxicity.

  • The gut microbiome was characterized via metagenomic sequencing in a subsample of n = 39 participants.
  • The difference in gut microbiome composition between survivors with and without CT was statistically significant (p = 0.02).
  • This finding suggests a potential link between chronic post-treatment toxicity and distinct microbial features.

Consumption of fruit and vegetables was inversely associated with anxiety symptoms in ICB-treated melanoma survivors.

  • The inverse association between fruit and vegetable consumption and anxiety was statistically significant (ρ = 0.3, p = 0.038).
  • Diet was assessed via questionnaire as part of participant screening.
  • This association was observed in the overall cohort of 48 survivors.

Added sugar consumption was correlated with the severity of experienced symptoms, including pain, fatigue, and shortness of breath.

  • Added sugar consumption was correlated with symptom severity with ρ = 0.4 and p = 0.003.
  • Pronounced associations were observed across the spectrum of symptoms, including pain, fatigue, and shortness of breath (p < 0.05 for each).
  • Diet was assessed via participant-completed screening questionnaires.
  • These associations were observed in the overall cohort of 48 long-term survivors.

The study enrolled long-term metastatic melanoma survivors who had initiated immune checkpoint blockade treatment at least 3 years prior and were no longer on treatment.

  • 48 patients were prospectively enrolled from a melanoma survivorship clinic.
  • Eligibility required initiation of ICB treatment at least 3 years earlier.
  • Participants were not currently on treatment at the time of enrollment.
  • Participants completed screening questionnaires for depression, anxiety, diet, and physical activity.

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Citation

Robert M, Saha S, Dizman N, Rohlfs M, Sirmans E, Simon J, et al.. (2026). Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes and the Microbiome in Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier.. Nutrients. https://doi.org/10.3390/nu18010040