Why are men more likely to develop multiple myeloma than women?

Researchers at the University of Alabama at Birmingham have identified significant sex-based differences in how multiple myeloma presents and progresses, findings that could influence clinical care for the second most common blood cancer in the United States.

The study, published in CANCER, analyzed 850 patients with newly diagnosed multiple myeloma from the Integrative Molecular And Genetic Epidemiology (IMAGE) study and conducted parallel analyses of two large population datasets: the SEER database (78,351 patients) and the Multiple Myeloma Research Foundation CoMMpass study (1,143 patients).

Men were more likely to present with International Staging System stage III disease and showed higher myeloma burden, including elevated serum monoclonal protein levels, greater rates of organ dysfunction—particularly kidney failure—and more extensive bone damage. Women were more likely to have low bone mineral density but generally had less severe disease at diagnosis. These differences remained after adjustment for age, race, body mass index, education, income, smoking history, and alcohol use.

Parallel analyses of SEER and CoMMpass data showed that women had consistently better overall survival and progression-free survival than men. The female survival advantage persisted after adjusting for age, disease stage, performance status, and treatment factors.

The investigators suggest several biological mechanisms that may underlie these sex differences. Chromosomal abnormalities linked to myeloma development appeared more frequently in younger males, and immune differences—such as higher frequencies of regulatory T cells in men—may contribute to worse clinical features and disease progression.

“This research suggests that sex-specific mechanisms promote multiple myeloma pathogenesis, which may account for the excess risk seen in men,” said lead author Krystle L. Ong of the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham. “These findings may be used to improve risk stratification, diagnosis, and tailored treatments for both men and women with newly diagnosed multiple myeloma or related early precursor conditions.”