Mediterranean diet correlates with responses to melanoma immunotherapy

According to the results of a cohort study published in JAMA Oncology.

“We need larger studies in more geographical areas to further elucidate the role of diet in the context of cancer immunotherapy,” according to a dietitian from the University of Groningen.

An alternative Mediterranean diet positively correlated with progression-free survival at 12 months (PFS-12; probability of 0.74; P = 0.01; false discovery rate [FDR], .021; effective degrees of freedom [edf]1.54) as well as the overall response rate (ORR; probability of 0.77; P = 0.02; RAD, .032; edf, 0.83).

“A Mediterranean diet is associated with positive responses to immune checkpoint blockade, a relatively new and effective treatment for serious cancers,” said lead author Laura A. Bolte, MSc, registered dietitian and PhD candidate in medicine from the Department of Gastroenterology and Hepatology at the University of Groningen and the University Medical Center Groningen in the Netherlands, said in a written comment to CancerNetwork^®. “These [immune checkpoint blockade] the drugs cause the immune system to recognize, eliminate and destroy cancer cells.

Bolte elaborated on the potential health benefits associated with a Mediterranean diet.

“These foods are important sources of fiber, unsaturated fats, antioxidants and polyphenols. Preclinical and functional studies have shown immunomodulatory and antitumor activities of these nutrients, in part via the gut microbiome,” Bolte said.

Investigators in this cohort study assessed the association between usual diet and responses to immune checkpoint blockade therapy for advanced melanoma. Researchers prospectively collected clinical and dietary data from patients enrolled in the PRIMM-UK trial (NCT03643289) and the PRIMM-NL/POINTING trial (NCT04193956).

Clinical endpoints of interest included ORR, PFS at 12 months, and immune system-related adverse events (IRAE). Investigators assessed IRAEs based on the CTCAE v5.0 criteria, focusing on the incidence of grade 2 or greater to avoid the interindividual variability associated with milder AEs.

Investigators assessed food intake using the EPIC-Norfolk Food Frequency Questionnaire and the Dutch Healthy Diet Food Frequency Questionnaire. Determining dietary quality in the patient cohorts involved the use of 4 food-based scores, including an Alternative Mediterranean Diet Score, an Original Vegetable Diet Index, a Healthy Vegetable Diet Index, and a Diet Index unhealthy plant.

The use of generalized additive logistic models determined whether higher adherence to a specific diet correlated with a higher likelihood of response or IRAE in patients.

The study included 44 patients from the PRIMM-NL trial and 47 patients from the PRIMM-UK trial. Most patients in each respective cohort had previously received a single PD-L1 inhibitor (73% vs. 51%). Most patients in PRIMM-NL had stage M1d disease (39%), and most of those in PRIMM-UK had stage M1c disease (36%).

In terms of food scores, the mean score was 3.07 (standard deviation [SD], 1.25) for the alternative Mediterranean diets, 30.52 (SD, 4.29) for the original plant-based diet index, 32.84 (SD, 5.81) for the healthy plant-based diet index, and 31 .70 (SD, 4.56) for the unhealthy vegetable diet index in the PRIMM-NL population. For the PRIMM-UK population, the respective mean dietary scores were 2.55 (SD, 1.28), 34.23 (SD, 4.45), 35.49 (7.37) and 34.32 (5 .65), respectively.

For the Alternative Mediterranean Diet scores, the log probability of being a responder increased by 1.43 for each unit increase in the Alternative Mediterranean Diet score. Training on the PRIMM-UK cohort and validation on the PRIMM-NL cohort predicted PFS at 12 months and ORR by alternative Mediterranean diet scores with an area under the curve of 0.70.

In a principal component analysis, the researchers noted a parabolic association of PC2 characterized by high fruit consumption with PFS at 12 months (P = 0.01; ADR, .018; fed, 2.14) and ORR (P = 0.01; ADR, .018; EDF, 2.7) in the PRIMM-NL population. No significant association was observed in the PRIMM-UK population.

Individual components of the Mediterranean diet, including monounsaturated and polyunsaturated fatty acids, wholemeal bread, vegetables and legumes, as well as vitamins C and E and β-carotene were positively associated with a similar response to diet score alternative Mediterranean. These associations, however, lacked statistical significance after several hypothesis testing corrections.

Investigators noted that fewer IRAEs occurred with a diet high in legumes, wholemeal bread, and magnesium. Additionally, there were more IRAEs associated with higher consumption of processed meat.

Bolte suggested how more widespread adoption of a Mediterranean diet could positively impact US patient populations while citing the need for more research to affirm the health benefits seen in his study.

“The traditional principles of a Mediterranean diet are the dietary principles most recommended by public health institutions around the world. Unfortunately, an increasing incidence of chronic diseases and cancers such as colorectal cancer have been observed alongside Westernization We need larger studies in multiple geographies to further elucidate the role of diet in the context of cancer immunotherapy,” Bolte concluded.

Reference

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