Abstract

The increasing incidence of geriatric patients with multiple myeloma has elevated concerns in clinical practice. While the introduction of novel therapeutic agents has substantially improved outcomes in younger patients with myeloma, poorer outcomes remain in older patients. Managing older patients requires a multidisciplinary team approach to consider factors that may influence both treatment selection and outcomes. Aging is associated with remodeling of vital organs, physiological downregulations of basal metabolism, susceptibility to multiple comorbidities with ultimate frailty, thereby contributing to the underrepresentation and exclusion of very old patients from clinical trials. Therefore, timely confirmation of a precise diagnosis is crucial for prompt initiation of treatment if the desired outcome is to be achieved. Adequate and judicious assessment using comprehensive geriatric assessment tools minimizes toxicities and treatment discontinuation. Initiating treatment with combinational therapy requires knowledge of indications and anticipated outcomes, as well as individualized therapy with appropriate dose-adjustment. Individualized therapy based on good clinical acumen and best practices obverts unwanted polypharmacy, preventing iatrogenic harm. This review will therefore address the approaches and challenges faced in managing myeloma in geriatric patients aged 80 years and older, highlighting recommended therapeutic strategies and future prospective regimens.

Highlights

  • Multiple myeloma (MM) is an incurable plasma cell neoplasm and is largely a disease of older adults

  • The analyses demonstrated that cytogenetics, impaired renal function, lung function, and Karnofsky Performance Status (KPS) improved the prediction of fit, intermediate-fit, and frail patients leading to the development of the “revised” myeloma comorbidity index (RMCI)

  • Carfilzomib plus cyclophosphamide and dexamethasone (KCd) for both induction and maintenance therapy in transplant-ineligible NDMM mitigated the poor prognosis carried by high-risk cytogenetics and yielded similar Progression-Free Survival (PFS) and overall survival (OS) in high-risk and standard-risk patients showing that prolonged carfilzomib use is a beneficial alternative for high-risk MM disease [84]

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Summary

Introduction

Multiple myeloma (MM) is an incurable plasma cell neoplasm and is largely a disease of older adults. The study showed significantly superior response rates, PFS and OS, and a favorable risk-benefit profile with VRd compared to the approved frontline regimen of Rd. In the subgroup analysis, VRd improved OS in patients older than 75 years with a median OS of 63 vs 31 months with Rd alone [53]. In the IFM 01/01 (phase III) trial, which investigated the use of MPT in NDMM patients older than 75 years, results showed a prolonged PFS of 18.5 to 24 months (p = 0.001) and OS of 29.1 to 44.0 months (p = 0.028) favoring the MPT regimen [63].

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