Moving Forward with Multiple Myeloma

PROJECT SUMMARY Multiple Myeloma (MM) is the second most common hematological malignancy in the U.S., typically diagnosed in older adults and disproportionately affecting African Americans (AA). Treatment advances, such as frontline autologous stem cell transplant (ASCT) and a growing list of novel therapies such as proteasome inhibitors, immunomodulatory drugs, and immunotherapies have changed MM from being an imminently fatal condition to that of a chronic disease, such that patients are now treated continuously. Five-year survival rates have increased from 32% to 58% over the last two decades. Pre-existing co-morbid conditions (e.g., obesity, hyperlipidemia, hyperglycemia), on-going treatment toxicity, symptom burden (e.g., fatigue), as well as bone instability, muscle loss, and immobility are common; all of which collectively and negatively impact physical, emotional, and social health. Physical functioning naturally decreases with age and is negatively associated with adverse body composition phenotypes. Consequently, as shown by our group and others, sarcopenia (low muscle mass and function) and/or sarcopenic obesity (low muscle mass and function plus high adiposity) are highly prevalent at MM diagnosis, and predict fatigue, increased risk of falls, and shortened overall survival. Therefore, lifestyle interventions targeting physical functioning would likely have numerous performance-based and patient-reported benefits for these survivors, yet this remains largely unexplored. Moving Forward with Multiple Myeloma, will examine the efficacy of a 16-week lifestyle intervention, on physical function (primary) and patient-reported outcomes (secondary) among 184 (24% Black/AA) individuals with stable MM. We will also explore associations between lifestyle behaviors and prognostic tissue (body composition), serum (indicators of metabolic health and inflammation), and novel cellular biomarkers (cell senescence). This trial is grounded in significant developmental work exploring the needs and interests of MM survivors and establishing a Patient and Community Advisory Board to guide the proposed work. We have assembled a highly qualified, multidisciplinary study team (behavioral scientist, nutrition scientist, physician-scientist, clinical exercise physiologist, patient-reported outcomes expert, biological aging expert, and biostatistician) and will leverage our extensive expertise in intervention trial implementation. We propose several biologically plausible mechanisms to explore how lifestyle behaviors work in concert to influence highly relevant outcomes for MM survivors. Thus, this study reflects a critical step in a research trajectory to help discern how lifestyle behaviors can assist myeloma survivors move forward in their journey toward better health as they live longer with the chronic burdens of their cancer and related therapies.