Mediterranean Diet May Improve Responses to Immune Checkpoint Blockade for Advanced Melanoma

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A recent study published in the Journal of the American Medical Association of Oncology¹ assessed the impact of patients with advanced melanoma adhering to a Mediterranean diet and the probability of response to immune checkpoint blockade (ICB) treatment. The study authors found that higher adherence to a Mediterranean diet was associated with a higher probability of response to treatment with ICB in patients with advanced melanoma.

"We found in our study that a Mediterranean dietary pattern is associated with a better response and progression-free survival, so survival after one year without further tumor progression,” said Laura Bolte, MSc, study author, dietician, and MD/PhD candidate at the University Medical Center Groningen in the Netherlands. “The Mediterranean diet is high in whole grains, legumes, fruits, vegetables, nuts, and fish, so healthy unsaturated fatty acids and low in processed foods, and especially red and processed meat. And what's interesting about this is that such a diet is high in nutrients, such as polyphenols, antioxidants, and fiber that have already been shown to have immunomodulatory actions in preclinical studies. This observation makes a lot of sense to us that it's also associated with it better immunotherapy response.”

In the cohort study, 91 patients in the UK and the Netherlands who received ICB between 2018 and 2021 for advanced melanoma were assessed for their dietary intake using the EPIC-Norfolk food frequency questionnaire and the Dutch Healthy Diet food frequency questionnaire. Four food-based scores were determined to address dietary quality across the cohort, including:

1. Alternate Mediterranean diet score (aMED)

2. Original plant-based diet index (oPDI)

2a. Healthy plant-based diet index (h-PDI)

2b. Unhealthy plant-based diet index (u-PDI)

“It's important to note that this was not an intervention study. We didn't put one patient group on a diet and the other on a control or placebo. But we did an observational study. So, we handed out dietary questionnaires to the patients. And those are called food frequency questionnaires. They ask patients about their dietary habits, such as what they ate in the last month. It has been shown that that's a good indication of long-term habitual diets. So their stable patterns, not what they ate the last weekend just before filling it in, but really, the long-term stable dietary patterns, and we assessed that before patients went on treatment. And then we correlated the dietary patterns that we identified to the response, and the response was assessed prospectively during the treatment,” noted Bolte.

Primary endpoints of the study included:

• Overall response rate (ORR)
• Progression-free survival at 12 months (PFS-12)
• Immune-related adverse events (irAEs)

Out of the 91 patients, 44 were Dutch with a mean age of 59.43 years; 47 patients were British with a mean age of 66.21 years. The aMED scores had the largest association with ORR (51%), PFS-12 (54%), and irAEs (24%). Both ORR and PFS-12 showed positive associations with the aMED score with a maximum score of 5 associated with the highest probability of response.

“This data shows melanoma and association between tumor response on immunotherapy and the type of food intake,” said Geke Hospers, MD, PhD, study author and professor and medical oncologist at the University Medical Center Groningen in the Netherlands. “This data makes sense when you think about a healthy gut, the immune system, the microbiome, and the mechanism of action of the immune checkpoint inhibition. Therefore, I think these data points make fellow clinicians less skeptical and they can take this knowledge into discussions with their patients so they have unique data. And I think this data can help us in thinking about how it works. That is very promising that all colleagues are less skeptical of this diet.”

The study concluded that food preferences and nutrient sources vary across geographic regions, which creates the need for multinational cohort studies combined with additional resolution on food compositions.

“The Mediterranean diet is, in essence, already the most recommended dietary pattern by global health institutions worldwide and also by cancer societies, such as the National Cancer Institute. Some implementations that we could think about to integrate diet more in oncology would be to have dietitians in your team of medical oncologists, but also to train medical doctors in important aspects of diet. I think that we all should have a good answer on what a healthy diet consists of for our patients. I also think that we have to move now to intervention studies, but that's something that you cannot do overnight; a lot of practical questions need to be addressed. If you just tell patients, 'that's our dietary advice, and then you observe changes in response, that might not be very effective in advanced cancer patients. So maybe we have to think about providing food boxes or providing meals through the hospital kitchen, and then follow up on the response,” concluded Bolte.

Reference

1. Bolte LA, Lee KA, Björk JR, et al. Association of a Mediterranean diet with outcomes for patients treated with immune checkpoint blockade for advanced melanoma. JAMA Oncol. Published online February 16, 2023. doi:10.1001/jamaoncol.2022.7753. https://jamanetwork.com/journals/jamaoncology/fullarticle/2801594