Defining the vulnerable patient with myeloma—a frailty position paper of the European Myeloma Network

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Abstract

As the treatment landscape continues to evolve towards the application of precision medicine in multiple myeloma (MM), there is a clear need to identify those patients who are at risk of not achieving the maximum benefit whilst exposed to the highest level of toxicity. This group of patients, defined as frail, is an unmet clinical need. However, how we define such a vulnerable group of patients with MM remains to be clarified. An integral aspect of this is to define the physiological age and capacity of patients with MM to deal with the burden of their disease and it’s treatment. Such assessments may include not only functional and clinical assessments but also laboratory-based biomarkers of frailty, aging and senescent cellular burden. A need to develop, test and validate clinical screening scores before their adoption into clinical practice is mandated. This position paper from the European Myeloma Network aims to review what is known about defining frailty in MM, and how we can advance this knowledge for the design of clinical trials and ultimately how we deliver treatment in the clinic.

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From discoveries in ageing research to therapeutics for healthy ageing

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For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan.

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Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN).

Pieter Sonneveld, Henk Lokhorst, Gareth J. Morgan … (2011)

Most patients with newly diagnosed multiple myeloma (MM) are aged > 65 years with 30% aged > 75 years. Many elderly patients are also vulnerable because of comorbidities that complicate the management of MM. The prevalence of MM is expected to rise over time because of an aging population. Most elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more susceptible to side effects and are often unable to tolerate full drug doses. For these patients, lower-dose-intensity regimens improve the safety profile and thus optimize treatment outcome. Further research into the best treatment strategies for vulnerable elderly patients is urgently needed. Appropriate screening for vulnerability and an assessment of cardiac, pulmonary, renal, hepatic, and neurologic functions, as well as age > 75 years, at the start of therapy allows treatment strategies to be individualized and drug doses to be tailored to improve tolerability and optimize efficacy. Similarly, occurrence of serious nonhematologic adverse events during treatment should be carefully taken into account to adjust doses and optimize outcomes.