November 15, 2023

Mount Sinai

A first-of-its-kind study unveils how diabetes drives multiple myeloma growth and differences in survival outcomes for Black versus white patients with both conditions

Samir Parekh, MD

Patients with multiple myeloma who also have diabetes have reduced overall survival when compared to those without diabetes. However, in a subgroup analysis, this difference in survival due to diabetes was seen in white patients but not in Black patients, according to a study published today in Blood Advances.

According to the Centers for Disease Control and Prevention, diabetes affects 13 percent of the U.S. population, and its prevalence is growing rapidly. Multiple myeloma, a cancer of blood plasma cells in the bone marrow, is the second most common blood cancer in the United States and disproportionately affects non-Hispanic Black adults, in whom it is the most common blood cancer.

“This study showed possible other treatment approaches by modifying patient risk factors: by controlling diabetes with diet or medications,” said one of the study’s senior authors, Samir Parekh, MD, Director of Translational Research in Multiple Myeloma and co-leader of the Cancer Clinical Investigation program at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. “This may be important in addition to multiple myeloma treatment for long term outcomes as well.”

Another senior author, Emily Gallagher, MD, PhD, Associate Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at Icahn Mount Sinai, said, “Our preclinical data from mouse models and the known increased risk for multiple myeloma in patients with diabetes suggest that diabetes may be a risk factor contributing to the increased development of multiple myeloma in Black individuals compared to white individuals. To our knowledge, this is the first study to show the mechanistic association between type 2 diabetes and multiple myeloma progression.”

While investigators have long been aware of the increased risk of multiple myeloma in patients with diabetes, this is the first study to examine racial disparities in survival rates among those living with these comorbid conditions.

“We knew from prior studies that patients with multiple myeloma and diabetes have lower survival rates,” said first author and senior author Urvi Shah, MD, a multiple myeloma specialist at Memorial Sloan Kettering Cancer Center. “But what we did not know is how these outcomes differ between races. Diabetes is much more common in Black individuals versus white individuals, and we wanted to understand whether this difference may play a role in health outcomes among patients with both conditions.”

The researchers conducted a retrospective study, collecting data from electronic health care records of 5,383 patients with multiple myeloma from two academic medical centers: Memorial Sloan Kettering Cancer Center and Icahn Mount Sinai. Fifteen percent of patients included had a diabetes diagnosis (12 percent of white and 25 percent of Black patients).

Across the board, the researchers observed that among patients with multiple myeloma, those with diabetes had poorer survival rates than those without. When analyzing results by race, however, they found that while white patients with multiple myeloma and diabetes had lower survival rates than those without diabetes, they did not observe this finding among Black patients.

“What we did not expect to see here was that diabetes was actually associated with worse survival outcomes among white individuals with myeloma, but not Black individuals,” said Dr. Shah.

Generally, one’s risk of developing diabetes increases with age. Study findings also show that overall survival decreased with age. Notably, however, in this cohort, diabetes was 50 percent more prevalent among Black patients 45-60 years old than white patients over 60. Younger patients may tolerate multiple myeloma treatments better than older individuals, and these differences could explain some of the racial differences investigators observed in survival outcomes.

When investigating the mechanisms behind these findings, the researchers observed that in genetically engineered mouse models, multiple myeloma tumors grew more rapidly in non-obese diabetic mice than in non-diabetic controls.

After studying the biological mechanisms underlying tumor growth in these mice, researchers found that an insulin-related signal was overactivated in the diabetic mice, leading them to believe that higher insulin levels associated with diabetes may accelerate cancer growth.

Of note, these findings do not account for how survival outcomes may be affected by the quality of care patients with diabetes receive. The researchers said more research was necessary on that point. Another limitation was that race was self-reported.

Going forward, the researchers aim to identify therapies that stop both the development of multiple myeloma and the overactive insulin signaling pathway they believe may be prevalent in patients with multiple myeloma and diabetes. Dr. Shah is also investigating how modifiable risk factors like the microbiome and one’s diet can be altered to improve cancer outcomes.

“While drugs are important, as oncologists, we need to also look at comorbidities and modifiable risk factors to improve patient survival outcomes. Therapies and lifestyle changes can go hand in hand,” Dr. Shah emphasized.