Plant-Based Diet, Stool Butyrate Associated with Long-Lasting MRD Negativity in Multiple Myeloma

A plant-based diet and stool butyrate production was associated with sustained minimal residual disease (MRD) negativity in patients with multiple myeloma undergoing treatment with maintenance lenalidomide (Revlimid), according to a study published in Clinical Cancer Research.

Those with α-diversity of the fecal biome at 3-months was higher in patients with sustained MRD negativity, with a median time of 16.9 months vs 11.9 months in those without. Patients who had a significantly higher relative abundance of predicted butyrate producers were more likely to have sustained MRD negativity with a median of 0.093 vs 0.054 (P = .025) in those without. Those who consumed protein from seafood or plants had a correlation with butyrate concentration at 3 months (P = .009) and sustained MRD negativity (P = .05).

Samples were collected from 74 patients, 59 of whom had habitual dietary pattern assessments and 49 had 16S sequencing of the stool microbiome. In 34 patients, there was an overlap of dietary assessment and stool examination, of whom 32 had stool butyrate concentration measurements. At enrollment, MRD status was assessed, with 42 patients being MRD-positive and 32 being MRD-negative.

MRD status was assessed in 68 patients at 12 months, 61 patients at 24 months, and 48 patients at 36 months. There was an association between sustained MRD negativity and MRD negativity at enrollment; of note, among the 32 patients with long-lasting negativity, 26 were MRD-negative at enrollment.

Prior to maintenance therapy, autologous hematopoietic stem cell transplantation (AHCT) was given to 45% of patients. Due to this, the timepoint for microbiome evaluation was 3 months to allow for the resolution of post-AHCT reduction in microbiome diversity.

In patients who had MRD negativity, the stool butyrate was significantly higher at 3 months at a median of 18.1 mmol/L vs 10.0 mmol/L in those who did not (P = .037). Of note, patients’ AHCT status was not associated with diversity (P = .82), a relative abundance of butyrate producers (P = .44), and stool butyrate concentrations (P = .99) at 3 months.

After adjusting for AHCT status, age, gender, and cytogenetics, stool microbiome α-diversity at (P = .004) and relative abundance of butyrate producers (P = .03) at 3 months sustained significance with regard to their association with long-lasting MRD negativity. Other factors not associated with MRD status included other stool metabolites such as acetate, propanoate,

valerate, heptanoate, isobutyrate, methylbutyrate, and isovalerate (P >.1). Additionally, there were weak associations with plasma CCL2 and IL33 in butyrate levels.

Diet was analyzed between the factors of diet composition, stool butyrate concentration, and subsequent MRD status. At 3 months, total protein (R = .5; P = .004), and seafood and plant protein (R = .45; P = .009) were linked to stool butyrate concentration. The investigators described seafood and plant proteins as seafood, nuts, seeds, soy products, and legumes.

The standard maximum score was 0.8 cup or less (P = .01) per 1000 kcal, and the standard minimum score was 0 (P = .05) and was correlated with MRD negativity. Additionally, those who consumed plant nutrients with antioxidant effects such as anthocyanidins (R = .47; P = .01), flavones (R = .48; P = .01), and flavonols (R = .42; P = .02), correlated with stool butyrate concentration.

Reference

Shah UA, Maclachlan KH, Derkach A, et al. Sustained minimal residual disease negativity in multiple myeloma is associated with stool butyrate and healthier plant-based diets. Clin Cancer Res. Published online September 28, 2022. doi:10.1158/1078-0432.CCR-22-0723