Patients with multiple myeloma who also have diabetes may experience worse overall survival outcomes compared with patients who don’t have diabetes, according to a recent study published by Shah et al in Blood Advances. The new findings demonstrated that the differences in survival may be dependent on race.
Background
Diabetes affects about 13% of the U.S. population, and its prevalence is growing rapidly. Multiple myeloma, the second most common blood cancer in the United States, disproportionately affects non-Hispanic Black patients—in whom it is the most common hematologic malignancy.
“This study showed possible other treatment approaches by modifying patient risk factors, by controlling diabetes with diet or medications,” explained co–senior study author 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,” he added.
“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,” emphasized co–senior study author Emily Gallagher, MD, PhD, Associate Professor of Medicine (Endocrinology, Diabetes, and Bone Disease) at the Icahn School of Medicine at Mount Sinai.
Study Methods and Results
In the new retrospective study, investigators used electronic health-care records to analyze the outcomes of 5,383 patients with multiple myeloma—15% of whom had been diagnosed with diabetes (12% of the White patients and 25% of the Black patients).
Disregarding race, the investigators found that the patients with multiple myeloma who had diabetes demonstrated poorer survival rates compared with those who didn’t have diabetes. When examining the outcomes by race, however, the investigators found that White patients with multiple myeloma and diabetes had lower survival rates than those without diabetes, whereas Black patients with multiple myeloma and diabetes did not have lower survival rates than those without diabetes.
“What we did not expect to see here was that diabetes was actually associated with worse survival outcomes among White [patients] with [multiple] myeloma, but not Black [patients],” highlighted first study author Urvi Shah, MD, a multiple myeloma specialist at the Memorial Sloan Kettering Cancer Center.
Further, the investigators discovered that overall survival rates decreased with age. Notably, diabetes was 50% more prevalent among Black patients aged 45 to 60 years than among White patients aged over 60 years. They noted that younger patients may tolerate treatment for multiple myeloma better than older patients, and that these differences could explain some of the racial disparities in survival.
Using genetically engineered mouse models, the investigators assessed the mechanisms behind the survival outcomes and found that multiple myeloma tumors grew more rapidly in diabetic mice without obesity than in nondiabetic controls. After studying the biological mechanisms underlying tumor growth in these mice, the investigators revealed that an insulin-related signal was overactivated in the diabetic mice—indicating that higher insulin levels associated with diabetes may accelerate cancer growth.
Conclusions
Although researchers have long been aware of the increased risk of multiple myeloma in patients with diabetes, this is one of the first studies to examine racial disparities in survival rates among those living with the comorbid conditions.
“We knew from prior studies that patients with multiple myeloma and diabetes have lower survival rates,” stressed Dr. Shah. “But what we did not know is how these outcomes differ between races. Diabetes is much more common in Black individuals vs White individuals, and we wanted to understand whether this difference may play a role in health outcomes among patients with both conditions,” she continued.
The investigators underscored that their new findings did not explain how survival outcomes may have been affected by the quality of care patients with diabetes received. However, more studies may be necessary to better understand other factors that may be influencing survival in these patient populations and to identify modifiable risk factors such as the microbiome and diet that can be altered to improve cancer outcomes.
Going forward, the investigators plan to identify novel therapeutics that can hinder both the development of multiple myeloma and the overactive insulin signaling pathway they believe may be prevalent in patients with the comorbid conditions.
“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 concluded.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
