Treatment of older adult or frail patients with multiple myeloma

Abstract

Older adults with multiple myeloma (MM) are a growing population, and personalizing treatment based on disease and health status is imperative. Similar to MM staging systems that provide disease-related prognostic information, myeloma-specific frailty tools can better identify subgroups at greatest risk for treatment-related toxicity and early treatment discontinuation, as well as predict overall survival. Several myeloma-specific validated tools are well studied. Although these fitness/frailty scores have shaped our understanding of the heterogeneity among older adults with myeloma, the application of such scores in treatment decision making (ie, transplant considerations, relapse) is an unmet need. Here we outline how to incorporate frailty assessments in the evaluation of older adults with MM in the clinical setting with consideration of other factors such as patient preferences, treatment risks/benefits, life expectancy, and disease biology.

Multiple myeloma with high-risk cytogenetics and its treatment approach

“…Parameters predicting poor outcomes are well established, including cytogenetic abnormalities (CAs) such as t(4;14), t(14;16), t(14;20), ≥ 3 copies of chromosome band 1q21 (1q21 +), deletion of chromosome arm 1p (del(1p)), and deletion of chromosome band 17p13 (del(17p)) (Table 1 ); clinical biomarkers and features such as ISS stage 3 [ 3 ], high serum lactate dehydrogenase (LDH) [ 4 ], the presence of circulating plasma cells including plasma cell leukemia (PCL) [ 5 ], central nervous system (CNS) involvement [ 6 ], and plasmablastic morphology [ 7 ]; and host factors such as age, renal dysfunction, and frailty [ 8 ]. Other molecular parameters can also predict outcomes (Table 1 ), such as gene expression profiling (GEP) signatures, including the GEP70-gene signature from University of Arkansas for Medical Sciences (UAMS) [ 9 ] and the EMC-92 signature from the HOVON group [ 10 ]; a gene mutational status such as APOBEC (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide)-type mutational signatures [ 11 ]; a high total number of mutations [ 12 ]; the presence of homologous recombination deficiency [ 13 ]; and the presence of chromothripsis [ 14 , 15 ].…”

More intensive therapy has a better effect for frail parents with multiple myeloma

“…The optimal intensity of treatment in adults who are frail with multiple myeloma (MM) is often uncertain, given the higher risk of harm in patients who are frail on standard, intensive regimens. 1 , 2 Randomized controlled trials (RCTs) directly or indirectly exclude patients who are frail, limiting the generalizability of results to a large portion of patients treated in practice. 3 , 4 Although analyses from RCTs and observational studies consistently show that frailty is associated with higher risks of treatment toxicity, treatment discontinuation, and mortality, 5 this evidence does little to inform the key clinical question, that is, whether to administer to patients who are frail, in practice, the same intensity of treatments evaluated in the younger, fitter patients in RCTs.…”

Decision-making factors for an autologous stem cell transplant for older adults with newly diagnosed multiple myeloma: A qualitative analysis

“…Although many pivotal ASCT randomized controlled trials (RCT) excluded older adults (3,4), several large retrospective studies and a meta-analysis have shown that ASCT is safe and feasible in selected older adults as per their local or study criteria (5,6). There are a wide variety of tools that may be used to evaluate a patient for ASCT including performance status, geriatric assessment tools and frailty indices (7,8); however, there a lack of agreement between these tools (9) and subsequently wide variation in their usage. Furthermore, there is wide heterogeneity in the eligibility of ASCT in older adults across different institutions and regions.…”