Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups

Abstract

Multiple myeloma (MM) is twice as common in Black individuals compared to White, and diabetes mellitus (DM) disproportionately affects Black patients. While numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (12% White and 25% Black). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (HR 1.27; 95% CI 1.11, 1.47; p<0.001). This appeared to be driven by a marked difference in OS between White patients with and without DM, but not Black patients. In contrast, obesity was associated with better OS in Black patients, but not White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised non-obese diabetic (Rag1-/-/MKR) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phospho-S6 ribosomal protein(Ser235/236) levels indicating greater activation of the mammalian target of rapamycin pathway. Our study is the first to evaluate racial differences in DM prevalence and survival in MM as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients, and to improve survival in MM DM management cannot be ignored.

Monoclonal Gammopathy of Undetermined Cardiovascular Significance; Current Evidence and Novel Insights

“…Although DM might be associated with the development of MM [16] and DM may be an adverse prognostic factor for overall survival in patients with MM [17], data linking DM and MGUS are limited, with conflicting conclusions due to the overlapping effect of obesity [18]. A population-based matched case-control study in Sweden, with 94,579 cases and 368,348 controls, aimed to examine the association between DM and plasma cell dyscrasias as well as lymphoproliferative disorders [19].…”

Deciphering racial disparities in multiple myeloma outcomes

“…In this issue of Blood Advances, Shah et al report a retrospective clinical study evaluating the impact of diabetes and obesity on survival among patients with multiple myeloma from 2 academic medical centers. 1 This study is among the first to evaluate the association separately in Black and White patients. Over a median follow-up of 4.6 years, the data showed that patients with multiple myeloma and preexisting diabetes had worse overall survival compared to patients with nondiabetic conditions, whereas patients with elevated body mass index (BMI ≥25 kg/m 2 ) had improved overall survival compared to those with BMI <25 kg/m 2 .…”

Post hoc analysis of daratumumab plus lenalidomide, bortezomib and dexamethasone in Black patients from final data of the GRIFFIN study

“…In contrast, obesity was associated with better overall survival in Black patients, but not in White patients. 15 Nevertheless, bortezomib is a component of standard MM treatment across lines of therapy, 16 and its use remains frequent in the real-world setting. Bortezomib dosing has evolved over the last few years from twice-weekly use, as described in this study, to weekly use.…”