A High-Fiber, Plant-Based Diet in Myeloma Precursor Disorders: Results from the NUTRIVENTION Clinical Trial and Preclinical Vk*MYC Model
Urvi A. Shah, Laura Lucia Cogrossi, Juan‐José Garcés, Anna Policastro, Francesca Castro, Andriy Derkach, Teng Fei, Susan DeWolf, Matteo Grioni, Sofia Sisti, Jenna Blaslov, Peter Adintori, Kinga Hosszu, Devin McAvoy, Mirae Baichoo, Justin R. Cross, Jenny Paredes, Aishwarya Anuraj, Sandeep Raj, Charlotte Pohl, Paola Zordan, Victoria Zinsmeyer, Rúben J. Ramos, Marco Lorenzoni, Brianna Gipson, Kylee Maclachlan, Ana Gradíssimo, Leonardo Boiocchi, Nathan Aleynick, Camilla Marchigiani, Sara Pagani, Erica Salehi, Richard P. Koche, Ronan Chaligné, Torin Block, Neha Korde, Carlyn Tan, Malin Hultcrantz, Hani Hassoun, Gunjan L. Shah, Michael Scordo, Oscar Lahoud, David J. Chung, Heather Landau, Jonathan U. Peled, Nicola Clementi, Marta Chesi, P. Leif Bergsagel, Sham Mailankody, Michaël Pollak, Anita D’Souza, Ola Landgren, Susan Chimonas, Sergio Giralt, Saad Z. Usmani, Neil M. Iyengar, Alexander M. Lesokhin, Marcel R.M. van den Brink, Matteo Bellone
Abstract
Consumption of a Western diet and high body mass index (BMI) are risk factors for progression from premalignant phenotypes to multiple myeloma, a hematologic cancer. In the NUTRIVENTION trial (NCT04920084), we administered a high-fiber, plant-based diet (HFPBD; meals for 12 weeks, coaching for 24 weeks) to 23 participants with myeloma precursor states and elevated BMI. The intervention was feasible and improved quality of life and modifiable risk factors: metabolic (BMI, insulin resistance), microbiome (diversity, composition), and immune (inflammation, monocyte subsets). Disease progression trajectory improved (n = 2) or was stable. Findings were translated to Vk*MYC mice modeling the myeloma precursor state, in which a high-fiber diet (HFD) delayed disease progression through improved metabolism and microbiome composition, leading to increased short-chain fatty acid production that reinvigorated antitumor immunity and inhibited tumor growth. These effects from fiber consumption were independent of calorie restriction and weight loss. A HFD is a low-risk intervention that may delay progression to myeloma. SIGNIFICANCE: A HFPBD in participants with precursor plasma cell disorders and an elevated BMI improved metabolic, microbiome, and immune biomarkers of disease. In a subset, it may delay progression to myeloma. In mouse models, a HFD delayed progression to myeloma independent of calorie restriction. See related commentary by Fairfield and Reagan, p. 623.