According to research reported at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, a link seems to exist between hematologic malignancies and dietary components. The speakers said their studies may ultimately lead to dietary interventions that could alter the course of certain cancers.

NUTRIVENTION: High-Fiber Diet = Less Progression to Myeloma

Urvi A. Shah, MD

Consumption of a high-fiber diet may slow the evolution of multiple myeloma from the precursor conditions monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma in some patients, in the NUTRIVENTION study, reported by Urvi A. Shah, MD, Assistant Attending Physician at Memorial Sloan Kettering Cancer Center, New York.¹ She noted that genomic alterations are known drivers of disease progression, but it is possible that lifestyle factors that affect immune function may also play a role.

“This was our hypothesis or question: Can we tilt the scale and reduce the risk for myeloma development if we normalize weight and blood sugar, improve diet quality, and improve the microbiome and immune system,” she said during a press briefing.

NUTRIVENTION examined the effect of diet in 20 patients meeting the diagnostic criteria for MGUS or smoldering myeloma and having a body mass index (BMI) > 25 kg/m². Study participants consumed plant-based, high-fiber meals for 12 weeks, most of which were shipped to them. The primary endpoint of the pilot study was feasibility, defined as more than 70% adherence to the meals and a BMI reduction greater than 5% at 12 weeks. Follow-up continued for a total of 52 weeks.

Adherence was 91% at 12 weeks and 58% at 52 weeks, with a mean BMI reduction of 7% at 12 weeks, which was maintained to 52 weeks. Patients also had favorable changes in a variety of biochemical markers, including insulin resistance, fecal microbiome diversity, and inflammation.

“We also saw that two patients with progressive disease had stabilization of the disease on the intervention,” Dr. Shah said. “Even though they are 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 the trajectory of the disease.”

Studies in mice from the Bellone laboratory are confirming the observations, showing that consumption of the high-fiber diet is associated with increased microbiome diversity, reduced growth rate of abnormal plasma cells (suggesting an effect on disease progression), reduced inflammation, and improved immune function.

Enrollment has begun in a follow-up trial (NUTRIVENTION-3; ClinicalTrials.gov identifier NCT05640843) of 150 patients with MGUS or smoldering myeloma. Participants will be randomly assigned to receive the high-fiber diet with or without supplements or placebo.

Study Finds High Fiber = Less GVHD

Researchers from City of Hope National Medical Center, Duarte, California, reported that consumption of a high-fiber diet by patients undergoing allogeneic stem cell transplantation was associated with increased overall survival and a decreased incidence of graft-vs-host disease (GVHD) through cultivation of a healthy gut microbiome.² The findings suggest that increasing dietary fiber, while adhering to the low microbial dietary recommendations, could serve as a strategy to reduce GVHD severity, said Jenny Paredes, PhD, staff scientist at City of Hope.

Jenny Paredes, PhD

Dr. Paredes and her team analyzed the diets of 173 patients, tracking all foods they consumed (totaling 35,228 meals) and calculating the nutrients from 10 days before until 30 days after transplant (totaling 3,837 days of tracking). They examined 101 non–cell-depleted patients, identifying 29 who developed lower gastrointestinal acute GVHD, and 29 who did not.

They found that higher fiber intake in patients after allogeneic hematopoietic cell transplantation was associated with an increase in overall survival, a decrease in the incidence of lower gastrointestinal acute GVHD, an increase in microbial diversity and producers of butyrate, and an increase in the fecal concentrations of short chain fatty acids.

In addition, the consumption of a 12% cellulose diet in a preclinical GVHD model led to an increase in microbial diversity, a decrease in pathogen relative abundance, an increase in Treg/T cell conventional ratio, and a decrease in GVHD lethality. “Based on our results, we conclude that dietary fiber could be used in the prevention of GVHD,” she said, adding that City of Hope will be implementing new nutrition protocols for patients undergoing transplantation.

Preclinical Trial of Ketogenic Diet Effect on Immunotherapy

Shan Liu, PhD

In a recent study in a preclinical mouse model, a ketogenic diet, which is high in fats and low in carbohydrates, was shown to boost the efficacy of chimeric antigen receptor (CAR) T-cell therapy.³ Shan Liu, PhD, a postdoctoral researcher at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues tested five diets: ketogenic, high-fiber, high-fat, high-protein, and a Western-style diet high in cholesterol and unhealthy fats. Mice fed the ketogenic diet demonstrated the best tumor control and longer survival than mice on the other diets. Dr. Liu co-led the study with Puneeth Guruprasad, PhD, who earned his PhD at Penn and is now a medical student in the Perelman School of Medicine. The lead authors worked under the mentorship of co-senior authors Marco Ruella, MD, Assistant Professor of Hematology-Oncology, a researcher with the Center for Cellular Immunotherapies, and Scientific Director of Penn Medicine’s Lymphoma Program; and Maayan Levy, PhD, Assistant Professor of Microbiology.

The researchers believe the key to the diet’s success is β-hydroxybutyrate (BHB), which is produced by the breakdown of fat during ketosis, which happens on a ketogenic diet. They discovered that BHB helps to fuel the CAR T cells in a manner that boosts their antitumor effects, apparently through genetic alterations. Mice who were directly treated with BHB during CAR T-cell treatment, ie, received two-prong therapy, mounted the strongest immune response and achieved the best outcomes. The group also looked at patients receiving CAR T-cell therapy for lymphoma and found that higher levels of BHB in the blood were linked to greater expansion of CAR T cells.

“Our study showed that the ketogenic diet enhanced the antitumor function of CAR T cells through BHB, and BHB boosted CAR T-cell expansion and cytokine release and improved CAR T-cell metabolic fitness, thereby strengthening the antitumor efficacy of CAR T cells. Encouraged by this result, we have initiated a clinical trial of BHB supplementation in non-Hodgkin lymphoma CAR T-cell patients,” Dr. Liu said.

EXPERT POINT OF VIEW

Ciara L. Freeman, MD, PhD

Ciara L. Freeman, MD, PhD, of Moffitt Cancer Center’s Blood and Marrow Transplant and Cellular Immunotherapy Department, Tampa, offered some thoughts on the findings of these studies on dietary factors and hematologic malignancies.

“The NUTRIVENTION study in myeloma precursors and the City of Hope study of diet during allogeneic transplant focus on different malignancies but both highlight the importance of gut health in cancer prevention and recovery. In both cases, the gut microbiome—whose bacteria are instrumental in digestion, immune function, and control of inflammation—was improved for the patients who ate more fiber. It appears that simple dietary changes, especially a focus on plant-based, high-fiber foods, could be a key part of cancer care,” she said.

Dr. Freeman continued: “Findings from the CAR [chimeric antigen receptor] T-cell study are incredibly exciting…. The demonstration that β-hydroxybutyrate, a metabolite of the ketogenic diet, enhances CAR T-cell function by improving metabolism and gene expression opens new avenues for integrating nutritional strategies into cancer treatment. While early, these results suggest that dietary interventions could potentially optimize outcomes for patients undergoing CAR T-cell therapy.”

She shared these concluding comments: “Although these findings are early, the studies point to a promising intersection of nutrition and both cancer prevention and treatment optimization.”

DISCLOSURE: Dr. Shah reported financial relationships with Sanofi, BMS, and Janssen. Dr. Paredes and Dr. Liu reported no conflicts of interest. Dr. Freeman reported financial relationships with ONK Therapeutics, Seattle Genetics, BMS, Janssen, AbbVie, Amgen, Sanofi, Celgene, and Incyte.

REFERENCES

1. Shah UA, Cogrossi LL, Derkach A, et al: A high-fiber dietary intervention (NUTRIVENTION) in precursor plasma cell disorders improves biomarkers of disease and may delay progression to myeloma. 2024 ASH Annual Meeting & Exposition. Abstract 671. Presented December 8, 2024.
2. Paredes J, Fei T, Dai A, et al: Increased fiber intake results in better overall survival and lower GI-aGVHD in allo-HCT recipients and pre-clinical GVHD models. 2024 ASH Annual Meeting & Exposition. Abstract 259. Presented December 7, 2024.
3. Liu S, Guruprasad P, Han K, et al: Ketogenic diet boosts CAR T-cell function via b-hydroxybutyrate. 2024 ASH Annual Meeting & Exposition. Abstract 4. Presented December 8, 2024.