Approach to the Older Adult With Multiple Myeloma

Abstract

Multiple myeloma (MM) is a disease of aging adults, and numerous therapeutic options are available for this growing demographic. MM treatment of older adults continues to evolve and includes novel combinations, new generations of targeted agents, immunotherapy, and increasing use of autologous stem cell transplantation (ASCT). Understanding age-related factors, independent of chronologic age itself, is an increasingly recognized factor in MM survivorship, especially in understudied populations, such as octogenarians. Octogenarians have inferior survival that cannot be explained by cytogenetic profiles alone. Incorporating assessments of geriatric factors can provide guidance on how to intensify or de-escalate therapeutic options. Functional status, using objective testing, is superior to traditional metrics of performance status and should be implemented to optimize the risk-benefit ratio of ASCT. ASCT is feasible and cost-effective, and chronologic age should not exclude ASCT eligibility. Upfront ASCT remains the standard of care, in the context of a sequential approach that includes pre-transplantation induction and post-transplantation maintenance. High-risk MM is classically defined by disease characteristics, yet shifting frameworks suggest that the high-risk designation could refer to any patient subgroup who is at risk for poorer outcomes—beyond disease-focused outcomes to patient-focused outcomes. Defining the optimal treatment of subgroups of older patients with high-risk disease on the basis of chromosomal abnormalities is unexplored. Here, we review tools to assess individual health status, explore vulnerability in octogenarians with MM, address ASCT decision-making, and examine high-risk MM to understand factors that contribute to survival disparities for older adults with MM.

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

“…However, the IMWG FS was tested, but not validated, in the setting of clinical intervention studies and thus, patients are selected according to strict inclusion criteria, which may limit "realworld" interpretation of the data (see below). More recently, the IMWG FS was tested in an unselected real-world population outside of a clinical trial setting demonstrating it can be used to define a more biologically frail population [31].…”

Shaping the Treatment Paradigm Based on the Current Understanding of the Pathobiology of Multiple Myeloma: An Overview

“…While most clinical studies incorporating upfront AutoSCT only enrol patients ≤65 years of age, in many jurisdictions, patients up to the age of 70–75 are actively considered for an AutoSCT. Based on a thorough assessment of frailty, performance status and comorbidities and in turn improved patient selection and supportive care measures, there is sufficient evidence that AutoSCT is both safe and effective in patients up to the age to 75 [ 80 , 81 ]. These transplant-eligible (TE) patients usually have induction therapy consisting of 4–6 cycles of triplet combination of an IMiD, PI (or an alkylating agent) with corticosteroid, followed by AutoSCT with/without consolidation, then maintenance.…”

<p>Updated Perspectives on the Management of Multiple Myeloma in Older Patients: Focus on Lenalidomide</p>

“…Reductions in lenalidomide dosing are recommended for less fit patients, and there are nonlenalidomide-based regimens included in the algorithm as well. 57 Trials to validate an approach using frailty measures to adjust are underway (NCT03720041). Individual patient characteristics, such as the presence of cognitive impairment, which may impact adherence to oral medication, or renal dysfunction, play a significant role when determining the treatment regimen for older adults with multiple myeloma, which emphasizes the need for an individualized approach.…”