Abstract
Simple SummaryChoosing the optimal therapy for elderly patients with multiple myeloma (MM) poses a difficult challenge for clinicians. Older patients are an extremely heterogeneous population, they are underrepresented in clinical trials, and data on octogenarians have been mainly limited to real-life settings. Treatment options for intermediate and frail patients might include dose-adapted combinations and less toxic combinations based on novel agents. Moreover, the discriminative power of the International Myeloma Working Group (IMWG) frailty score in detecting frailty and vulnerability could be improved by combining together aging-related factors (performance status, comorbidities, functional status) with disease-related factors (International Staging System stage, cytogenetic risk). Objective parameters could improve the reproducibility of this score and limit the subjectivity determined by patient-reported questionnaires on functional evaluations. Efforts are ongoing to simplify the IMWG frailty score and expand its use in real-life clinical practice.Multiple myeloma (MM) mostly affects elderly patients, which represent a highly heterogeneous population. Indeed, comorbidities, frailty status and functional reserve may vary considerably among patients with similar chronological age. For this reason, the choice of treatment goals and intensity is particularly challenging in elderly patients, and it requires a multidimensional evaluation of the patients and the disease. In recent years, different tools to detect patient frailty have been developed, and the International Myeloma Working Group frailty score currently represents the gold standard. It identifies intermediate-fit and frail patients requiring gentler treatment approaches compared to fit patients, aiming to preserve quality of life and prevent toxicities. This subset of patients is underrepresented in clinical trials, and studies exploring frailty-adapted approaches are scarce, making the choice of therapy extremely challenging. Treatment options for intermediate-fit and frail patients might include dose-adapted combinations, doublets, and less toxic combinations based on novel agents. This review analyzes the available tools for the assessment of frailty and possible strategies to improve the discriminative power of the scores and expand their use in real-life and clinical trial settings. Moreover, it addresses the main therapeutic challenges in the management of intermediate-fit and frail MM patients at diagnosis and at relapse.
Highlights
Multiple myeloma (MM) is mainly a disease of the elderly, with a median age at diagnosis of70 years
This review provides an overview of available strategies to assess patient frailty and of treatment management options for intermediate-fit and frail elderly patients
The IMWG frailty score allowed clinicians to delve into the complexity of frailty in MM
Summary
Multiple myeloma (MM) is mainly a disease of the elderly, with a median age at diagnosis of. Cancers 2020, 12, 3106 agents has resulted in a substantial survival improvement of MM patients, and the recent advent of immunotherapy has further increased survival rates This benefit appears to be more consistent in younger patients, it has been observed in patients aged ≥65 years, who have been traditionally considered ineligible for high-dose therapy and transplantation. 10–15% of patients, and approximately 10% of patients aged 80 years and older experience toxic deaths [8,9,10,11]. Given these premises, choosing the optimal MM therapy for elderly patients poses a difficult challenge for clinicians. This review provides an overview of available strategies to assess patient frailty and of treatment management options for intermediate-fit and frail elderly patients
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