High-fiber diet may slow progression of precursor conditions to multiple myeloma
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Key takeaways:
- The diet intervention appeared safe and feasible.
- It also improved quality of life and exhibited favorable effects on modifiable risk factors.
SAN DIEGO — A high-fiber plant-based diet may delay progression of certain precursor conditions to multiple myeloma, according to study results presented at ASH Annual Meeting and Exposition.
The intervention also improved biomarkers of the disease, results of the NUTRIVENTION trial showed.
The findings of both in vivo and clinical study support the potential anti-inflammatory role of this dietary approach, offering insights into how the relationship between diet, microbiota and immune modulation could slow progression of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma, researchers concluded.
“I think this is very empowering to patients in the sense that they feel like they have something within their control,” Urvi A. Shah, MD, hematologic oncologist and faculty member in the myeloma division at Memorial Sloan Kettering Cancer Center, told Healio. “Even if they decide eventually they want to consider a pharmacologic treatment, this is a low-risk action they can take on their own that may help reduce risk for progression, and I think that is a major benefit.”
Background
At least 3% of adults aged 50 years or older in the United States have MGUS or smoldering myeloma, according to study background. More than 70% of people with these disorders have overweight or obesity, more than 45% have prediabetes or diabetes, and fewer than 5% consume enough dietary fiber daily.
Approximately 1% of patients with MGUS progress to multiple myeloma each year. The rate is about 10% per year for those with smoldering myeloma, Shah said.
Prior research has identified several factors that may contribute to progression of MGUS or smoldering myeloma to multiple myeloma, according to study background. These include high BMI, poor diet, microbiome dysbiosis, insulin resistance, immune dysfunction and inflammation.
Epidemiologic studies suggested plant-based diets may reduce risk for MGUS and multiple myeloma. However, no study had examined whether a dietary intervention could affect modifiable risk factors and slow progression of these precursor conditions.
“Our question was whether we could tip the scale and reduce risk for myeloma development if we normalized weight and blood sugar, improved diet quality and improved the microbiome,” Shah said.
Methods
NUTRIVENTION — a single-arm, single-center pilot trial —included 20 people with MGUS or smoldering myeloma who had BMI of 25 kg/m2 or higher.
Trial participants received a high-fiber plant-based dietary intervention for 12 weeks — with a majority of meals provided — followed by 24 weeks of health coaching.
During the dietary intervention period, trial participants ate to satiety and had no calorie restriction.
Feasibility — defined as adherence of at least 70% — and BMI reduction of greater than 5% at 12 weeks served as the primary endpoint. Secondary endpoints or exploratory endpoints included metabolic markers, quality of life, and microbiome and immune profiling in bone marrow and peripheral blood.
Key findings
At baseline, trial participants had been consuming 20% of calories from unprocessed plant foods. This increased to 92% during the intervention period and remained significantly higher at 1 year than at baseline, Shah said.
Despite the lack of calorie restriction, researchers observed sustained BMI reduction of 7%, which persisted 1 year after trial initiation, Shah said.
Trial participants exhibited improved quality of life based on global health status.
The intervention exhibited favorable effects on modifiable risk factors, including reductions in fasting insulin levels — despite no change in carbohydrate intake — as well as increased gut microbiome alpha diversity and increased gut microbiome butyrate producers. Results showed an inverse association between BMI and gut microbiome alpha diversity.
The intervention reduced inflammation and improved anti-tumor immunity, Shah said. Researchers observed reductions in neutrophil count and C-reactive protein.
Single-cell RNA sequencing on bone marrow and flow cytometry on peripheral blood showed an increase in anti-inflammatory classical (CD14) monocytes and a decrease in inflammatory non-classical (CD16) monocytes.
Two patients — a 71-year-old man with MGUS and a 61-year-old woman with smoldering myeloma — achieved a reduction in long-term progression trajectory. Baseline data showed “clearly rising” levels of monoclonal protein — often called M spike — but those levels stabilized during the intervention.
“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change trajectory of the disease,” Shah said in an ASH press release.
Researchers also performed an in vivo study of transgenic Vk*MYC mice with smoldering myeloma that had received either a high-fiber or control diet.
Investigators monitored mice for progression to active multiple myeloma, and they used microbiome 16S sequencing and flow cytometry to assess differences in microbiome response profiles based on diet.
The high-fiber diet slowed progression from smoldering myeloma to multiple myeloma, with a more than doubling of median PFS between the intervention and control groups (30 weeks to 12 weeks).
Forty percent of mice given a high-fiber diet did not progress to multiple myeloma, whereas all mice in the control group progressed to myeloma.
Researchers observed microbiome and immune changes in mice consistent with those observed in human trial participants.
Next steps
Investigators surveyed trial participants and learned most considered the dietary intervention “easy” or “very easy,” Shah said. No participant considered it “difficult.”
Researchers reported high levels of adherence to the dietary approach, reaching 91% during the first 3 months and remaining at 58% after 1 year.
“Patients are motivated when they see the benefits,” Shah told Healio. “Even if it does not work in terms of reducing their risk for progression to multiple myeloma, it can reduce risk for other outcomes that we know greatly affect people with cancer, such as diabetes and cardiovascular disease.”
Researchers acknowledged the study findings are limited by the small sample size, which makes it difficult to determine why some participants saw changes in disease progression and others did not.
The follow-up NUTRIVENTION-3 trial, designed to compare a plant-based diet with supplements and placebo for people with MGUS or smoldering myeloma, is about 50% enrolled, Shah said. Preliminary data should be available in the next year or two, she said.
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Shah UA, et al. Abstract 671. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.
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