TY - JOUR
T1 - The prevalence and outcomes of frail older adults in clinical trials in multiple myeloma
T2 - A systematic review
AU - Mian, Hira
AU - McCurdy, Arleigh
AU - Giri, Smith
AU - Grant, Shakira
AU - Rochwerg, Bram
AU - Winks, Erica
AU - Rosko, Ashley E.
AU - Engelhardt, Monika
AU - Pawlyn, Charlotte
AU - Cook, Gordon
AU - Jackson, Graham
AU - Bringhen, Sara
AU - Facon, Thierry
AU - Larocca, Alessandra
AU - Zweegman, Sonja
AU - Wildes, Tanya M.
N1 - Funding Information: HM is the recipient of a Research Early Career Award from Hamilton Health Sciences Foundation. Funding Information: HM: Consultancy/Honoraria fees from GSK, Janssen, BMS/Celgene, Forus therapeautics, Amgen, Takeda, Sanofi; Research Funding from Janssen. AM: Honoraria/Advisory fees: GSK, Janssen, BMS/Celgene, Forus therapeutics, Amgen, Takeda, Sanofi; Research funding: BMS/Celgene. SG: Research funding from PackHealth CareVive and Sanofi. Honorarium from Carevive and OncLive. SJG: Supported by National Comprehensive Institute Grant No. (5-K12-CA120780-13; PI: William Kim) and National Institute on Aging Grant No. (1 R03 AG074030-01; PI: Shakira Grant). BR: None. EW: None. AER: Honoraria from Onclive, CurioScience, Medscape, I3Health. ME: None. CP: Honoraria from BMS/Celgene, Janssen, Sanofi; Consultancy fees from Abbvie, BMS/Celgene, Janssen, Sanofi. GC: No relevant COI. GJ: Honoraria from Takeda, BMS, Pfizer, Amgen J and J, GSK, and Oncopeptides. SB: Honoraria from Celgene, Amgen, Janssen, and Bristol Myers Squibb; Consultancy fees from Janssen, Takeda, Celgene, and Bristol Myers Squibb; Board of Directors or Advisory Committees for Celgene, Amgen, Janssen, GlaxoSmithKline, Sanofi. TF: No relevant COI. AL: Honoraria from and served on the advisory boards for Janssen-Cilag, Bristol Myers Squibb, Amgen, Takeda, Oncopeptides, GlaxoSmithKline, Sanofi, and Karyopharm. SZ: Research funding from Janssen, Takeda; Advisory Board for Janssen, Takeda, BMS, Oncopepties, Sanofi. TMW: Consulting fees from Carevive Systems, Sanofi; Research funding from Janssen. Publisher Copyright: © 2022, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes.
AB - Multiple myeloma (MM) is an incurable blood cancer that primarily affects older adults. Several frailty tools have been developed to address the heterogeneity of aging in this population. Uptake of these measures has been variable, leading to a gap in knowledge regarding the proportion of enrolled trial participants considered frail and uncertainty in the treatment-related effects and outcomes among this high-risk population. We performed a systematic review of therapeutic interventional MM clinical trials reporting on frailty. We included 43 clinical trials (24 randomized controlled trials and 19 non-randomized trials) which met eligibility criteria. Frailty was increasingly incorporated in studies in more recent years with 41.9% of included studies being reported in the last two years. Commonly used frailty tools included the International Myeloma Working Group (IMWG) frailty index (41.8%), and the simplified frailty score (39.5%). Frailty status was categorized with 3 levels as (frail, intermediate fit, or fit) in 51.2% of the studies and dichotomized (frail, non-frail) in 18.6% of studies. Frailty prevalence greatly varied across trials ranging from 17.2% to 73.6% of the cohort. Of the included studies, 72.0% conducted subgroup analysis (planned or post-hoc) based on frailty status. Most studies demonstrated a consistent benefit of MM interventions among the frail and non-frail populations, however in general, frail patients had worse outcomes compared to the fit. Although frailty is increasingly being incorporated in MM clinical trials, due to the variation in both the definition and categorization of frailty, there remains heterogeneity in the prevalence of frailty and its potential associated impact on outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85145514962&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41408-022-00779-2
DO - https://doi.org/10.1038/s41408-022-00779-2
M3 - Article
C2 - 36599867
SN - 2044-5385
VL - 13
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 1
M1 - 6
ER -