A new study has identified sex-specific differences in the clinical presentation, tumor burden, and survival outcomes of multiple myeloma (MM), the second most common blood cancer in the United States, which occurs at higher rates in men than in women. The research suggests that sex-specific mechanisms may influence MM pathogenesis and could inform improvements in risk stratification, diagnosis, and the development of tailored treatments.
Study Overview
The investigation, led by Krystle L. Ong, PhD, of the O'Neal Comprehensive Cancer Center at the University of Alabama at Birmingham (UAB), was published in CANCER, a peer-reviewed journal of the American Cancer Society. Researchers primarily analyzed data from 850 patients newly diagnosed with multiple myeloma who were enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE) study at UAB. Parallel analyses were also conducted using two large population-based datasets: the SEER database, comprising 78,351 MM patients, and the Multiple Myeloma Research Foundation CoMMpass study, which included 1,143 patients.
Key Clinical Differences
The study identified several distinct clinical features when comparing male and female patients:
- Disease Stage: Male patients demonstrated a higher likelihood of advanced (International Staging System stage III) disease at diagnosis.
- Myeloma Burden: Men presented with a higher myeloma load, indicated by elevated serum monoclonal protein, and in some analyses, kappa light chain disease.
- Organ Dysfunction: Male patients exhibited more instances of organ failure, particularly kidney failure, and increased bone damage.
- Bone Mineral Density: Conversely, men were less likely than women to have low bone mineral density.
- Myeloma-Defining Features: The specific features defining myeloma tended to differ between sexes.
These disparities in clinical presentation persisted even after adjusting for various demographic and lifestyle factors, including race, age, body mass index, education level, income, smoking history, and alcohol consumption.
Survival Outcomes
Broader survival data from the SEER database and the CoMMpass study indicated that women consistently demonstrated better overall survival and progression-free survival compared to men. This female survival advantage remained evident after adjusting for age, disease staging, performance status, and treatment factors.
Potential Biological Explanations
The research suggests several potential biological factors contributing to these observed sex differences:
- Chromosomal Abnormalities: Analyses indicated that certain chromosomal abnormalities, which are linked to the initiation and development of myeloma, are observed more frequently in younger males.
- Regulatory T Cells (Tregs): Men typically have higher frequencies of regulatory T cells (Tregs), which have been associated with adverse clinical features and disease progression in multiple myeloma.
Implications and Future Research
The findings suggest that sex-specific mechanisms promote multiple myeloma pathogenesis and may account for the increased risk and differing disease presentation observed in men. This research may contribute to improved risk stratification, diagnosis, and the development of tailored treatments for individuals with newly diagnosed multiple myeloma or related early precursor conditions. The authors also noted that age is an important driver for select pathologic genomic events that differ at the presentation of disease by sex, and future studies are needed to confirm these findings and further understand the relevant sex-specific mechanisms underlying multiple myeloma pathogenesis.