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Multicenter Study
. 2023 May 1;9(5):705-709.
doi: 10.1001/jamaoncol.2022.7753.

Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma

Laura A Bolte  1   2 , Karla A Lee  3 , Johannes R Björk  1   2 , Emily R Leeming  3 , Marjo J E Campmans-Kuijpers  1 , Jacco J de Haan  4 , Arnau Vich Vila  1   2 , Andrew Maltez-Thomas  5 , Nicola Segata  5   6 , Ruth Board  7 , Mark Harries  8 , Paul Lorigan  9 , Elisabeth G E de Vries  4 , Paul Nathan  10 , Rudolf Fehrmann  4 , Véronique Bataille  3   11 , Tim D Spector  3 , Geke A P Hospers  4 , Rinse K Weersma  1
Affiliations
Multicenter Study

Association of a Mediterranean Diet With Outcomes for Patients Treated With Immune Checkpoint Blockade for Advanced Melanoma

Laura A Bolte et al. JAMA Oncol. .

Abstract

Importance: Immune checkpoint blockade (ICB) has improved the survival of patients with advanced melanoma. Durable responses are observed for 40% to 60% of patients, depending on treatment regimens. However, there is still large variability in the response to treatment with ICB, and patients experience a range of immune-related adverse events of differing severity. Nutrition, through its association with the immune system and gut microbiome, is a poorly explored but appealing target with potential to improve the efficacy and tolerability of ICB.

Objective: To investigate the association between habitual diet and response to treatment with ICB.

Design, setting, and participants: This multicenter cohort study (the PRIMM study) was conducted in cancer centers in the Netherlands and UK and included 91 ICB-naive patients with advanced melanoma who were receiving ICB between 2018 and 2021.

Exposures: Patients were treated with anti-programmed cell death 1 and anti-cytotoxic T lymphocyte-associated antigen 4 monotherapy or combination therapy. Dietary intake was assessed through food frequency questionnaires before treatment.

Main outcomes and measures: Clinical end points were defined as overall response rate (ORR), progression-free survival at 12 months (PFS-12), and immune-related adverse events that were grade 2 or higher.

Results: There were a total of 44 Dutch participants (mean [SD] age, 59.43 [12.74] years; 22 women [50%]) and 47 British participants (mean [SD] age, 66.21 [16.63] years; 15 women [32%]). Dietary and clinical data were prospectively collected from 91 patients receiving ICB between 2018 and 2021 for advanced melanoma in the UK and the Netherlands. Logistic generalized additive models revealed positive linear associations between a Mediterranean dietary pattern that was high in whole grains, fish, nuts, fruit, and vegetables and the probability of ORR and PFS-12 (probability of 0.77 for ORR; P = .02; false discovery rate, 0.032; effective degrees of freedom, 0.83; probability of 0.74 for PFS-12; P = .01; false discovery rate, 0.021; effective degrees of freedom, 1.54).

Conclusions and relevance: This cohort study found a positive association between a Mediterranean diet, a widely recommended model of healthy eating, and response to treatment with ICB. Large prospective studies from different geographies are needed to confirm the findings and further elucidate the role of diet in the context of ICB.

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Conflict of interest statement

Conflict of Interest Disclosures: Drs Bolte, Björk, and de Haan reported grants from the Seerave Foundation during the conduct of the study. Dr Leeming reported personal fees from Zoe Ltd outside the submitted work. Dr Campmans-Kuijpers reported grants from Seerave Foundation during the conduct of the study as well as personal fees from Takeda and Janssen outside the submitted work. Dr Segata reported grants from the Seerave Foundation during the conduct of the study as well as personal fees from Zoe outside the submitted work. Dr Board reported funding for conferences and paid speaker fees from BMS, MSD, and Novartis. Dr Lorigan reported personal fees from BMS, Merck, Novartis, GSK, Amgen, Chugai, PierreFabre, NeraCare, Roche, and OncologyEducationCanada outside the submitted work. Dr de Vries reported institutional financial support from NSABP, Daiichi Sankyo, and Crescendo Biologics; grants from Amgen, Genentech, Roche, CytomX, G1 Therapeutics, Bayer, Synthon, Regeneron, Crescendo Biologics, GE Healthcare, and AstraZeneca; and service as a member of the ESMO-MCBS working party, chair of the ESMO Cancer Medicines Working Group, cochair of the RECIST committee, and member of expert panel for selection of the Essential Medicine List for the World Health Organization outside the submitted work. Dr Spector reported being a founder of and shareholder in Zoe Ltd outside the submitted work. Dr Hospers reported grants from the Seerave Foundation during the conduct of the study as well as personal fees from Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, Sanofi, and Pierre Fabre and grants from Bristol Myers Squibb. Dr Weersma reported personal fees from Takeda Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Association Between Overall Response Rate (ORR) and the Alternate Mediterranean Diet Score (aMED) Across Both Cohorts
The y-axis shows the probability of ORR on a scale from 0 to 0.9. The x-axis shows adherence to a Mediterranean diet high in vegetables, legumes, fruit, and whole grains and low in red and processed meat, expressed by the aMED score ranging from 0 (minimum score) to 5 (maximum score).
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