Table 3 Non-randomized controlled trial of therapeutic agents in multiple myeloma incorporating or reporting on frailty.
Study Name | Setting | Therapeutic agents | Median age | Frailty definition | Frailty categories | Frailty prevalence | Frailty based outcomes* | |
|---|---|---|---|---|---|---|---|---|
Newly-diagnosed MM | ||||||||
1 | Bao et al. (2021) [43] | Multicentre, China, (N = 95/120), ongoing, phase unknown | Two arms: Ixa/Lipodox/Dex or Ixa/Len/Dex If ≥ PR, Ixa/Dex maintenance | 71 | Study entry criteria: frail as per IMWG or Mayo geriatric vulnerability scoring system | Not applicable | Not applicable | IAd vs IRd PFS 16 vs NR OS NR vs NR ORR 80.9% vs 81.0% ≥ Grade 3 heme tox: 13.7% |
2 | Nakazato et al. (2021) [40] | Multicenter, Japan, phase II (N = 47) | Bort/Cyclo/Dex X 4 followed by Bort/Thal/Dex X 4 (dose for frailty) | 75 | Drug dosing: Vulnerable Elders Survey (VES-13) | Fit (VES-13 < 3), Frail (≥ 3) | 31 (66.0%) | 3 yr PFS 53.3% 3 yr OS 77.6% ORR 87.1% |
3 | Stege et al. (2021) | Multicentre, Europe, phase II (N = 65) | Ixa/Dara/Dex X 9 followed by Ixa/Dara for 2 years | 81 | Study entry criteria: IMWG frail pts, IMWG intermediate fit patients, longitudinal assessment | Not applicable | Not applicable | PFS 13.8 1 year OS 78% ORR 78% (induction) ≥ Grade 3 heme tox 31% ≥ Grade 3 non-heme 74% |
4 | Multicentre, Europe, phase II, (N = 238) | Bort/Mel/Pred X 9 | 77 unfit 81 frail | Subgroup included: IMWG frailty score plus other GA parameters; longitudinal assessment | Fit, unfit, frail | 61.0% | OS 31 Tx discontinuation 51% Unfit superior QoL than frail | |
5 | PI: Davis, Tyler (2020) Actively Recruiting (MMY2035) [53] | Multicentre, USA (N = 44) phase II | Dara/Len/Dex | Not available | Study entry criteria: IMWG intermediate fit and frail Drug dosing: adjusted for frailty | Not applicable | Not available | Not available |
6 | PI: Cohen, Yael (2019) Recruitment completed [62] | Multicentre, Israel (N = 41), phase II | Carf/Dara/Len/Dex | Not available | Subgroup included: fit, intermediate fit, frail as per IMWG Drug dosing: adjusted for frailty | Fit, intermediate fit, frail | Not available | Not available |
7 | Larocca et al. (2018) [52] | Multicentre, Europe, (N = 58), phase II | Carf/Cyclo/Dex X 9 followed by Carf maintenance | 71 | Subgroup included: IMWG frailty score | Fit, unfit, Frail | 10 (17.2%) | Not available |
8 | Tuchman S et al. (2017) [21] VCD lite | Single centre, United States, phase II, N = 14 (closed due to slow accrual) | Bort/Cyclo/Dex followed by bort/len maintenance | 76.5 | Subgroup included: Cancer and Aging Research Group Geriatric Assessment | Risk score from 0-19 | Median score 10 | Not applicable as continuous score |
9 | PI: Yoshihara, Satoshi (2017) Recruitment pending [63] | Single centre, Japan, (N = 30 target), Phase unknown | -Dara/Len/Bort/Dex (Ixa/len/dex if not tolerable) X 12 followed by maintenance | Not available | Drug dosing: IMWG adjusted for frailty | Not available | Not available | Not available |
10 | Larocca et al. (2016) [64] | Multicentre, Italy (N = 152), Phase II | Sequential 1.Bor/Mel/Pred 2. Bor/Cyclo/Dex 3. Bort/Pred | 78 | Subgroup included: IMWG | Fit, unfit, frail | 82 (54%) | PFS 13.8 months 2 year OS 60% ORR 65% Drug related SAE ≥ 13% |
Relapsed/Refractory | ||||||||
11 | PI: Touzeau, Cyrille (2021) recruiting, IFM 2021_03 [35] | Multicentre, Europe, (N = 80 target), Phase II | Ixa/Iberomide/Dex | Not available | Subgroup included: simplified frailty score | Not available | Not available | Not available |
12 | Macro et al. (2021) IFM 2018-02 [36] | Multicentre, Europe, phase II (N = 44/50 enrolled) | Ixa/dara/methylpred | 82 | Study entry criteria: frail as per IMWG and simplified frailty score | Not applicable | Not applicable | PFS not available OS not available ORR 86% in those continuing tx and 71% stopped tx |
13 | Lee et al. (2020) KMMWP-164 [37] | Multicentre, South Korea, phase II (N = 55) | Pom/Cyclo/Dex | 74 | Subgroup included: Simplified frailty score | Nonfrail, frail | 31 (56.4%) | PFS 7.36 months OS 18.48 months |
14 | PI: Ho Sup Lee, Kosin (2019) Recruiting [39] | Multicentre, Korea, Phase II (N = 102) | Len/Dex | Not available | Study entry criteria: R-MCI, Inadequate (intermediate), frail | Not applicable | Not available | Not available |
15 | Waldschmidt et al. (2018) VERUMM [38] | Single centre, Germany Phase I/II (N = 33) | Bort/Dox/Dex/Vorinostat | 62 | Subgroup included, Longitudinal assessment: R-MCI, IMWG, Kaplan Feinstein Index, Timed up and go, cognitive testing | Not available | Not available | Subset of frailty score improved from baseline to end of treatment |
16 | Ludwig et al. [65]. (2018) | Multicentre, Europe, Phase II (N = 90) | Ixa/Thal/Dex X 8 followed by Ixa maintenance | 67.3 | Subgroup included: Secondary endpoint IMWG frailty index | Fit, unfit, frail | Not available | PFS 10.9 OS Not reached |
17 | PI: Unknown (2018) Active, not recruiting [66] | Multicentre, China, (n = 30), phase unknown | Ixazomib | Not available | Subgroup included/secondary outcome, IMWG | Fit, unfit, frail | Not available | Not available |
18 | Nakazato et al. (2014) Recruitment status unknown Personalized BiRd [23] | Single Centre, Japan (n = 20), phase unknown | Clarithro/Len/Dex Len dose adjusted according to frailty | Not available | Drug dosing: according to VES-13 | Fit (VES-13 < 3) and Frail (VES-13 ( ≥ 3) | Not available | Not available |
19 | Mele et al. (2010) [22] | Single centre, Italy (N = 18), phase unknown | Bort/Cyclo/Dex | 76 | Study entry criteria: ≥ 1 geriatric syndromes, or more moderate–severe comorbidities, and (WHO) PS > 2 | Not applicable | Not available | Not available |
