The skinny on obesity and plasma cell myeloma: a review of the literature

Abstract

Despite tremendous advances in treatments for myeloma in the past decade, the disease remains incurable in the majority of patients. Here, we review recent data demonstrating an association between obesity and increased risk of myeloma development. This may be due to the pro-inflammatory cytokine profile caused by obesity. Currently, there are no screening or prevention strategies for myeloma, but we propose that obesity-associated inflammatory pathways, or obesity itself, may be amenable to intervention, thereby preventing the transition from pre-malignancy to myeloma. In addition, we suggest that the morbidity, mortality and the significant costs associated with myeloma treatment could be reduced by addressing modifiable risk factors, and that research efforts should explore this novel hypothesis. INTRODUCTIONOver the past several decades, the prevalence of obesity has increased markedly in the United States. 1 Today, two-thirds of the adult population in the United States is overweight (defined as body mass index (BMI) = 25 kg/m 2 and o 30 kg/m 2 ) or obese (BMI 30 kg/m 2 ). 2 A BMI greater than 25 kg/m 2 is associated with increased all-cause mortality. 3,4 This increased risk exists even in the absence of typically-measured metabolic abnormalities, suggesting that there is no 'benign phenotype' for obesity. 5 A substantial number of these premature obesity-related deaths is due to cancer. 6,7 Although the common solid tumor malignancies have received much attention, data from case-control and prospectively followed cohort studies have also demonstrated a positive association between obesity and plasma cell myeloma incidence and death. 7,8

Assessing the effect of obesity-related traits on multiple myeloma using a Mendelian randomisation approach

“…2 In addition to being a potential risk factor for MM, some, but not all, studies have suggested an association between BMI and prognosis. 1, 3 A recent study has suggested the relationship between BMI and MM may be through reduced levels of plasma adiponectin, the inflammatory mediator secreted by adipocytes.…”

Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities

“…Increasing evidence now indicates a link between obesity and myeloma incidence [152]. In fact, leptin levels were found to be increased in the serum of non-obese myeloma patients, with concentration correlating with disease progression [153].…”

Obesity and neoplasms of lymphohematopoietic cells

“…Several of the cytokines (eg, leptin and interleukin-6), increased in obese subjects, can act directly on myeloma and myeloid cells through ligand-receptor interactions regulating proliferative rate and or apoptosis. 9,29,31,32 Clonal hematopoiesis of indeterminate potential is now an accepted concept. [37][38][39] Individuals with such clones have an increased likelihood of progression to an overt myeloid malignancy, usually myelodysplasia or acute myelogenous leukemia.…”

“…The evidence for an increased risk of myeloma as a result of overweight and obesity is compelling. [3][4][5][6][7][8][9][10][11] Of special interest is whether the precursor of myeloma, essential monoclonal gammopathy (also known as monoclonal gammopathy of unknown significance), has an increased risk of occurrence in obese patients. An initial study indicated that it did, 11 whereas a recent study has challenged that finding.…”

“…23,24 The possible mechanisms underlying the relationship of overweight and obesity to the incidence of myeloma and the myelogenous leukemias are under study. 9,10,[25][26][27][28] It is unclear whether the metabolic, inflammatory, and endocrine effects of obesity, including decreased serum adiponectin, 26,28 elevated serum interleukin-6, 29 elevated serum leptin, [30][31][32][33] elevated serum insulin growth factor-1, 34,35 upregulation of the promyelocytic leukemia protein, 36 and other cytokines altered in the obese, 9 play a role in this relationship. Several of the cytokines (eg, leptin and interleukin-6), increased in obese subjects, can act directly on myeloma and myeloid cells through ligand-receptor interactions regulating proliferative rate and or apoptosis.…”