Multiple Myeloma: Fitness, Frailty & Improving Survival

The landscape of multiple myeloma treatment is shifting, moving beyond simply extending life to prioritizing the quality of that life. As more effective therapies emerge, and people live longer with the disease, understanding a patient’s overall “fitness” – their ability to tolerate treatment and maintain daily function – becomes paramount. This isn’t just about age; it’s about a complex interplay of physical and psychological factors. Recent research is focusing on how to accurately assess this fitness, and how to tailor treatment plans accordingly, even for those considered frail.

Beyond Age: Defining Fitness in Myeloma

Traditionally, age was a primary driver of treatment decisions in multiple myeloma. However, improvements in disease management, as noted in a 2022 report in Hematology, are leading to longer progression-free and overall survival rates, meaning physicians are seeing more patients for subsequent lines of therapy over extended periods. This means a patient’s chronological age is less important than their physiological age – their actual functional capacity.

“Fitness” in this context isn’t about running marathons. It’s about a patient’s resilience, their ability to withstand the side effects of treatment, and their capacity to recover. Frailty, conversely, represents a state of increased vulnerability. Recognizing the difference is crucial because treatment choices for younger patients are often focused on achieving the deepest, most durable response, while for older or frail patients, minimizing toxicity and maintaining quality of life take center stage.

The International Myeloma Working Group Frailty Score

To better quantify this concept of fitness, clinicians are increasingly turning to standardized assessments. The International Myeloma Working Group Frailty Score (IMWG FS) is a myeloma-adapted geriatric assessment clinical scoring system. It provides a more objective way to evaluate a patient’s overall health status, considering factors beyond just age and disease stage. This allows for a more nuanced approach to treatment planning.

Quality of Life Gains in Frail Patients: Findings from HOVON123

Recent findings from the HOVON123 clinical trial, published in the European Journal of Cancer in August 2024, offer encouraging news. The study focused on newly diagnosed multiple myeloma (NDMM) patients aged 75 and older, treated with Melphalan-Prednisone-Bortezomib (MPV). Researchers found that health-related quality of life (HRQoL) improved in both intermediate-fit and frail patients during initial treatment. Notably, frail patients experienced faster and larger improvements in HRQoL compared to their intermediate-fit counterparts. These improvements persisted even during post-treatment follow-up.

This challenges the assumption that frail patients will inevitably experience a decline in quality of life due to treatment toxicity. The study highlights the importance of not refraining from treating frail patients out of fear of worsening their HRQoL. The HOVON123 trial used two HRQoL instruments – the EORTC QLQ-C30 and -MY20 – to assess patient well-being before, during, and after treatment. The trial’s design involved nine dose-adjusted cycles of MPV, and HRQoL was measured at multiple time points to track changes over time.

Understanding HRQoL Assessments

Health-related quality of life (HRQoL) assessments, like those used in the HOVON123 trial, are crucial for understanding the patient experience. They go beyond simply measuring disease progression or survival rates. These assessments typically cover physical, emotional, social, and functional well-being, providing a holistic view of how treatment impacts a patient’s life. The EORTC QLQ-C30 is a generic HRQoL questionnaire, while the EORTC QLQ-MY20 is specifically designed for myeloma patients, focusing on symptoms and side effects related to the disease and its treatment.

The Link Between Frailty and Treatment Toxicity

Traditionally, frailty in NDMM patients has been linked to increased treatment-related toxicity, which, in turn, negatively affects HRQoL. However, the HOVON123 study suggests that with careful treatment selection and monitoring, even frail patients can experience meaningful improvements in their quality of life. This underscores the need for individualized treatment approaches that consider a patient’s overall fitness level.

What Comes Next: Refining Assessments and Tailoring Treatment

The growing recognition of the importance of fitness and frailty in myeloma management is driving several key areas of development. Researchers are working to refine and validate frailty assessment tools, making them more accurate and easier to employ in clinical practice. There’s also a growing emphasis on developing treatment strategies specifically tailored to the needs of frail patients, potentially involving lower doses of chemotherapy or alternative therapies with fewer side effects. Further research is needed to identify biomarkers that can predict treatment response and toxicity in frail patients, allowing for even more personalized treatment plans.

Ongoing clinical trials, like HOVON123, continue to gather data on the impact of different treatment regimens on HRQoL in frail and intermediate-fit patients. These trials will help to refine treatment guidelines and improve outcomes for this vulnerable population. The focus is shifting from simply extending survival to ensuring that patients can live longer, healthier, and more fulfilling lives, even in the face of a challenging diagnosis.