Influence of high-fiber diet on ipilimumab-induced gastrointestinal toxicity in metastatic melanoma

Abstract

Background: The anti-cytotoxic T-lymphocyte-associated protein (CTLA)-4 antibody ipilimumab (ipi) and the anti-programmed death (PD)-1 antibody nivolumab (nivo) are routinely used to treat metastatic melanoma. One of the most frequent severe immune-related adverse events (irAEs) induced by ipi is diarrhea as a symptom of ir-colitis. Here, the composition of the gut microbiome was shown to correlate with the risk of developing colitis. Stimulated by a patient case and the knowledge that nutrition influences the gut microbiome, we performed a retrospective analysis to evaluate dietary habits and the frequency of colitis in patients with ipi ± nivo therapy.

Methods: Patients with metastasized stage III or IV melanoma who were treated with ipi ± nivo and who were willing to take part in a nutritional survey and interview at least three months after the first ipi dose were included into the study. Dietary habits were investigated using the food frequency questionnaire (FFQ) and personal interviews. The calculated daily intake of calories, carbohydrates, fats, proteins, sugars, and dietary fiber was correlated with the development of ir-colitis.

Results: 20 patients were included into this study, and all but one received ipi-nivo combination therapy. The median age was 59.5 years, and 60 % were male. 4 of 20 patients (20 %) developed ir-colitis grade 3 after two cycles in the median and were managed with at least high-dose corticosteroids. The FFQ and interview were conducted in a median of six months after treatment initiation. In general, the interviewed patients followed a typical western-pattern diet based on carbohydrates as the main, followed by fat as the second most important energy substrate. Comparing patients with and without colitis our investigation revealed that the achieved amount of recommended dietary fiber intake per total energy intake (TEI) was negatively associated with diarrhea and colitis (p = 0.061). No significant differences concerning daily intake of calories, carbohydrates, fats, proteins, and sugar were found. In addition, no significant differences were found among patients in terms of their age, gender, tobacco use, supplement intake, therapy regime, or body mass index (BMI).

Conclusions: This pilot study gives first hints that nutritional habits might influence treatment tolerability to ipi ± nivo therapy. A high-fiber diet might protect against ir-colitis and diarrhea in ipi-treated patients. This observation should be validated by a prospective randomized interventional trial. However, if it is possible to prevent ir-colitis by a high-fiber diet that would be of great impact on routine patient treatment.

Keywords: Colitis; High-fiber diet; Immune checkpoint inhibitor; Immune-related adverse event; Melanoma; Nutrition.