New study reveals a fiber diet may delay a type of blood cancer
Researchers from Memorial Sloan Kettering Cancer Center to present the latest advances in blood cancer during The American Society of Hematology 2024 annual meeting
Meeting AnnouncementToday researchers at Memorial Sloan Kettering Cancer Center (MSK) reported results from the first ever clinical trial to show that a high fiber plant based dietary intervention may delay progression to multiple myeloma, a type of rare, incurable blood cancer affecting the bone marrow. The study enrolled 20 participants with a precancerous blood disorder and an elevated body mass index (BMI) at risk for developing multiple myeloma. They received 12 weeks of high fiber plant-based meals and 24 weeks of coaching. Two participants with progressing disease prior to study showed a significant improvement of their disease progression trajectory. Additionally, at one year after enrollment, none of the participants had progressed to multiple myeloma. MSK myeloma specialist and NUTRIVENTION study lead, Urvi Shah, MD, presented these findings at the 2024 American Society of Hematology (ASH) annual meeting in San Diego, California.
"This study showcases the power of nutrition—specifically a high fiber plant-based diet—and unlocks a better understanding of how it can lead to improvements in the microbiome and metabolism to build a stronger immune system,” said Dr. Shah. “These findings further support how we as physicians can empower patients, especially those with precancerous conditions, with knowledge on reducing their cancer risk through dietary changes.”
Multiple myeloma is the second most common blood cancer and typically arises from precursor conditions called monoclonal gammopathy of undetermined significance (MGUS) and smoldering (symptomless) myeloma. Recent studies have shown an increased risk of multiple myeloma in individuals with poor diet quality and reduced intake of plant foods. Additionally, individuals with these conditions and an elevated body mass index (BMI) are twice as likely to progress to multiple myeloma as people with these conditions and a normal BMI. With this information, researchers have been looking for ways to intervene before these conditions can progress to cancer.
During the study, participants were encouraged to eat as much as they wanted if it was whole plant-based foods such as fruits, vegetables, nuts, seeds, whole grains, and legumes. With these dietary changes there were significant improvements in quality of life, insulin resistance, gut microbiome health and inflammation. On average, participants lost eight percent of their body weight after 12 weeks. Following these positive results, Dr. Shah is currently enrolling for a larger, multi-center study with 150 participants called NUTRIVENTION-3.
These findings were confirmed in a smoldering myeloma mouse model where 44% of mice fed the high fiber diet did not progress to myeloma compared to the standard diet where all mice progressed to myeloma.
Funding for this trial was provided by the American Society of Hematology, the National Cancer Institute, the Allen Foundation Inc, the Paula and Rodger Riney Foundation, the Solomon Fund, the Italian Association for Cancer Research, and the Leukemia and Lymphoma Society.
Keto diet metabolite may power up CAR T cells to kill cancer
Laboratory studies reveal a potentially low-tech intervention to improve personalized cell therapy
University of Pennsylvania School of Medicine
SAN DIEGO – A simple dietary supplement may provide a new approach to boost CAR T cell function, according to a study from researchers in the Perelman School of Medicine at the University of Pennsylvania and Penn Medicine’s Abramson Cancer Center. While the approach needs to be assessed in clinical trials, the early research, shared in a press briefing today at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 4), hints at a potentially cost-effective strategy to improve CAR T cell function and cancer-fighting abilities.
CAR T cell therapy is a personalized treatment approach, pioneered at Penn Medicine, that reprograms patients’ own immune cells to kill their cancer.
“Thousands of patients with blood cancers have been successfully treated with CAR T cell therapy, but it still doesn’t work for everyone,” said co-lead author Shan Liu, PhD, a postdoctoral fellow who presented the study at ASH. “We took an outside-the-box approach to improve CAR T cell therapy, by targeting T cells through diet rather than further genetic engineering.”
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, an assistant professor of Hematology-Oncology, a researcher with the Center for Cellular Immunotherapies and the scientific director of Penn Medicine’s Lymphoma Program; and Maayan Levy, PhD, an assistant professor of Microbiology.
CAR T cells prefer BHB as a fuel source
First, the research team tested the effect of several different diets, including ketogenic, high-fiber, high-fat, high-protein, high cholesterol, and a control diet, on CAR T cell’s tumor-fighting capabilities using a mouse model of diffuse-large B-cell lymphoma. They found improved tumor control and survival in the mice receiving a ketogenic diet compared to all other diets. In subsequent studies, they found higher levels of beta-hydroxybutyrate (BHB), a metabolite produced by the liver in response to a ketogenic diet, was a key mediator of this effect.
The research builds on previous work from Levy’s team, which found that BHB strongly suppressed the growth of colorectal tumors in lab experiments.
“Our theory is that CAR T cells prefer BHB as a fuel source rather than standard sugars in our body, such as glucose,” Guruprasad said. “So, increasing the levels of BHB in the body gives the CAR T cells more power to take out the cancer cells.”
Translational studies in patient samples and healthy volunteers
Next, the research team tested a BHB supplement combined with CAR T cell therapy in laboratory models of human cancer (on a standard diet); the results showed complete obliteration of the cancer in the vast majority of mice and resulted in higher CAR T cell expansion and activation. To see if BHB, which occurs naturally at various level in our bodies, had a similar effect in humans, the team assessed blood samples from patients who had recently received CAR T cell therapy and found that greater BHB levels were associated with better CAR T cell expansion in patients. They also looked at T cells of healthy volunteers who took a BHB supplement and found similar changes in how normal T cells generated energy after exposure to BHB.
Past studies across several cancer types have looked at the impact of dietary interventions, such as a high-fiber diet, on the response to cancer immunotherapy, however the mechanism behind the BHB effect in this study appears to stem from metabolic changes in the blood, rather than via the gut microbiome, as in the case of a high-fiber diet.
Next steps and potential impact
The theory that BHB supplementation could improve response to CAR T cell therapy is being tested in a Phase I clinical trial at Penn Medicine’s Abramson Cancer Center.
“We’re talking about an intervention that is relatively cheap and has low toxicity potential,” Levy said. “If the clinical trial data pans out, I’m excited to think about how a fairly simple approach like this could be combined with dietary interventions or other, more traditional approaches, to enhance the anti-cancer effect.”
The clinical trial, led by principal investigator Elise Chong, MD, an assistant professor of Hematology-Oncology, will soon begin enrolling patients with relapsed or refractory large B-cell lymphoma who are receiving commercially available anti-CD19 CAR T cell therapy as part of their treatment.
“As a physician and scientist, I share my patients’ excitement for potential new strategies to better treat their cancer, and I’m thrilled to see this research move from the lab bench to translational studies and now to a clinical trial,” Ruella said. “However, we want to emphasize that, at this point, the research is still preliminary, and we’re not making any dietary or supplement recommendations to patients based on this study until we have definitive clinical evidence.”
The study was partly funded by the Penn-CHOP Microbiome Core.
Liu will present the findings during the Plenary Scientific Session on Sunday, Dec. 8 at 2 p.m. PT in the San Diego Convention Center Hall B.
Patients interested in clinical trials at the Abramson Cancer Center can search open clinical trials here or call 1-855-216-0098 to speak with a clinical trial navigator.
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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
The Perelman School of Medicine is consistently among the nation's top recipients of funding from the National Institutes of Health, with $550 million awarded in the 2022 fiscal year. Home to a proud history of “firsts” in medicine, Penn Medicine teams have pioneered discoveries and innovations that have shaped modern medicine, including recent breakthroughs such as CAR T cell therapy for cancer and the mRNA technology used in COVID-19 vaccines.
The University of Pennsylvania Health System’s patient care facilities stretch from the Susquehanna River in Pennsylvania to the New Jersey shore. These include the Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center, Chester County Hospital, Lancaster General Health, Penn Medicine Princeton Health, and Pennsylvania Hospital—the nation’s first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.
Penn Medicine is an $11.1 billion enterprise powered by more than 49,000 talented faculty and staff.
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