Mediterranean diet boosts response to immune checkpoint blockade therapy for melanoma

Adhering to a Mediterranean diet appears to increase the likelihood of responding to immune checkpoint inhibitors among patients with advanced melanoma, according to data from the PRIMM study.

The diet was associated with favourable immune checkpoint blockade therapy outcomes, with the highest probability of treatment response seen at the highest alternate Mediterranean diet (aMED) score. The probability values were 0.74 for progression-free survival at 12 months (PFS-12; p=0.01) and 0.77 for objective response rate (ORR; p=0.02). [JAMA Oncol 2023;doi:10.1001/jamaoncol.2022.7753]

For each unit increase in the aMED score, the log odds of responding to treatment increased by 1.43.

“Individual components of the Mediterranean diet, including monounsaturated and polyunsaturated fatty acids, whole-meal bread, vegetables, legumes, and potatoes, followed a similar positive association with response as the aMED score, as did vitamins C and E and β-carotene. However, these associations were not significant after multiple hypothesis testing correction,” the investigators pointed out.

“Similarly, we observed fewer immune-related adverse events (irAEs) with high legume, whole-meal bread, and magnesium consumption but more irAEs with higher processed meat intake,” they added.

A widely recommended model of healthy eating, the Mediterranean diet is low in processed foods and meat and is rich in plant-derived foods, whole grains, fish, nuts, fruit, legumes, and vegetables. The investigators believe that the diet may influence immunotherapy response by way of the gut microbiome.

Several preclinical studies found several nutrients, including fibre, polyphenols, and antioxidants to have immunomodulatory and antitumour activities, which are mediated via the gut microbiome, they noted. [Nat Med 2022;28:2344-2352; Cancer Discov 2022;12:1742-1759; Sci Transl Med 2020;12:eaay8707; Gut 2022;71:734-745]

Meanwhile, the Mediterranean diet has been associated with an increased abundance of bacteria producing short-chain fatty acids (SCFAs) that have been shown to be predictive of immunotherapy response in several studies. Indeed, a published cohort of 52 patients treated with immune checkpoint inhibitors for different solid tumours, high faecal SCFA concentrations were linked to longer PFS. [Gut 2021;70:1287-1298; Nat Med 2022;28:535-544; JAMA Netw Open 2020;3:e202895]

“Immune checkpoint blockade has improved the survival of patients with advanced melanoma. Durable responses are observed for 40–60 percent of patients, depending on treatment regimens. However, there is still large variability in the response to treatment with [the therapy], and patients experience a range of immune-related adverse events of differing severity,” according to the investigators.

“The findings [from PRIMM] suggest a potential role for diet in improving responses to immune checkpoint blockade treatment outcomes,” they added.

PRIMM included 91 patients (mean age at diagnosis 62.93 years, 59.34 percent men) with advanced melanoma. They were given antiprogrammed cell death 1 and anticytotoxic T lymphocyte–associated antigen 4 monotherapy or combination therapy. Dietary intake was assessed through food frequency questionnaires.