Exploring Cross-Sectional and Longitudinal Associations Among DNA Methylation, Prognostic Proteins, and Symptoms in Patients Prescribed Oral Anticancer Medications for Multiple Myeloma

At-home administration of oral anticancer medications (OAM) limits interactions with healthcare providers, therefore limiting opportunities for symptom management, posing threats to medication adherence. Individuals diagnosed with multiple myeloma (MM) experience symptoms from both disease- and treatment-related factors. Proteins Beta-2 Microglobulin (B2M) and Lactate Dehydrogenase (LDH) are routinely used in disease monitoring, yet their associations with symptoms and regulation via DNA methylation (DNAm) in individuals with MM have not been investigated. This study explored relationships among LDH and B2M proteins; DNAm of genes B2M, LDHA, LDHB ; and symptoms in patients prescribed OAMs for MM. This was a 6-month, longitudinal, exploratory analysis. Symptoms were assessed using self-reported measures. Protein levels were extracted from medical records. DNAm of B2M, LDHA, and LDHB promoter regions were quantified via pyrosequencing of peripheral blood samples. Linear mixed modeling explored cross-sectional and longitudinal associations. Significant cross-sectional associations were identified between fatigue, LDHA and B2M DNAm, and B2M protein ( p < .02); pain and LDHA and B2M DNAm ( p < .05); gastrointestinal disturbances and LDHA DNAm and LDH protein ( p < .05); shortness of breath and LDHA DNAm ( p < .04); and depression and LDH protein ( p < .04). Longitudinal interaction effects were significant for B2M DNAm and fatigue ( p < .05), LDHA and B2M DNAm and pain ( p < .04), and LDH protein and depression ( p < .04). Prognostic proteins B2M and LDH and their gene-level DNAm patterns were significantly associated with symptoms in individuals taking OAMs for MM. These preliminary findings support further exploration of multi-omics pathways underlying symptoms to inform symptom identification and management strategies.