Disparities in multiple myeloma
Multiple myeloma is the malignant clonal proliferation of plasma B cells in the bone marrow and, despite the advent of new therapies, remains incurable and generally fatal. It progresses from the more common but often subclinical precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to overt and symptomatic multiple myeloma. Racial disparities have been observed in all stages of the disease, and as compared with Whites, individuals who are Black have a higher risk of MGUS and myeloma and a higher mortality rate.11 They have not experienced the same survival gains seen in White patients.
Some research suggests that these disparities may be more related to socioeconomic status as opposed to race. One analysis of 562 patients found that those with higher socioeconomic status had a median overall survival of 62.8 months compared with 53.7 and 48.6 months for middle and low socioeconomic status (P = 0.015).12
After controlling for confounders including race, patients with low socioeconomic status had a 54% increase in mortality rate relative to those with high status. The authors then performed a similar analysis of 45,505 patients with multiple myeloma from the Surveillance, Epidemiology and End Results-18 database to support their analysis, and that also showed low socioeconomic status to be independently associated with poorer overall survival.
“In some homogeneous health systems, such as the VA, we are seeing that Black patients do as well or better than White patients,” said Catherine Marinac, PhD, an assistant professor of medicine, Harvard Medical School, Boston. “Survival is equal or better, as long as treatment is not delayed and they receive the standard of care.”
Black patients generally have a more indolent disease subtype and may experience less aggressive disease, but they have not experienced the same magnitude in survival as White patients following the introduction of new therapeutics. This disparity lends support to the influence of socioeconomic factors, such as unequal access to novel therapies and/or differences in treatment response, and lower rates of autologous stem cell transplantation.13
However, there are racial/ethnic differences in risk for both myeloma and its premalignant conditions, as well as incidence. Blacks have a twofold increased risk of myeloma compared with White individuals and are diagnosed at younger ages. Differences in myeloma incidence is less marked in other racial/ethnic groups, such as Hispanics, where it is only slightly higher than in Whites at 6.7 per 100,00.11 In contrast, the incidence of myeloma is markedly lower in Asians as compared with non-Hispanic Whites (incidence rate of 3.8 versus 6.2 per 100,000). Black persons also have a markedly higher prevalence of MGUS, and these differences suggest that biology, and clinical characteristics, differ by race or ancestry.
“Mortality among Black patients is also higher,” said Dr. Marinac, who is also on the faculty in the division of population sciences at the Dana Farber Cancer Institute, also in Boston. “The higher mortality rate is driven by the higher incidence.”
There are also differences in the prevalence of immunoglobulin isotypes observed across racial/ethnic groups of MGUS patients, Dr. Marinac explained, which is consistent with the hypothesis that there is a biological basis for disparities arising in precursor lesions.
“What we are looking at now is cancer prevention and early intervention,” she said. “There are well-defined precursors to myeloma, and Blacks are three times more likely to have a precursor condition.”
Early detection of precursors followed by preventing progression to full-blown multiple myeloma is one way of addressing disparities, but right now, there are no real screening guidelines. “Most patients now are diagnosed incidentally, and then the only intervention is to monitor them,” Dr. Marinac said. “At Dana Farber, we are now looking to see if we can refine screening, and then see who may need additional monitoring.”
The Promise study, being conducted at Dana Farber, is recruiting participants to examine the molecular changes that occur when precursor conditions develop into full-blown multiple myeloma and is open to individuals considered to be at high risk: Black race and/or have a first-degree relative with multiple myeloma or one of its precursor conditions.
Dr. Marinac also pointed out that there are ongoing clinical trials that are looking at low-risk early interventions in patients with precursor conditions. “We are now looking at lifestyle and metformin,” she said. “The thought is that if we treat them now, we can prevent myeloma from developing.”