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V. Montefusco et al.
1.23, 95%CI: 0.64-2.37; P=0.54) (Figure 1A). Median PFS2 and 5- year PFS2 were 43.2 months (95%CI: 37.0-52.4) and 38% (95%CI: 31-47%) in PO, 27.9 months (95%CI: 4.9-NR) and NR in EMP, and 46.4 months (95%CI: 44.1-48.9) and 40% (95%CI: 37-43%) in non-EMD patients (Figure 3).
Overall survival. Median OS was 63.5 months (95%CI: 48.2- 84.7) and 79.9 months (95%CI: 75.8-88.3; P=0.01) in EMD and non-EMD patients, respectively. Five-year OS was 51% (95%CI: 45-58%) and 59% (95%CI: 57-61%) (P=0.01) in EMD and non- EMD patients, respectively (Online Supplementary Figure S4), and there was a significant difference between PO and non-EMD (HR 1.39, 95%CI: 1.13-1.70; P=0.001) (Figure 1B). In multivariate analysis the presence of EMD was associated with a reduced OS (HR 1.41, 95%CI: 1.16-1.71; P<0.001), in line with other known prognostic factors: high risk versus standard cytogenetic (HR 1.68, 95%CI: 1.44-1.96; P<0.001), ISS III versus I (HR 2.36, 95%CI: 1.98- 2.82; P<0.001) (Online Supplementary Figure S5). Type of therapy did not impact on OS: IMiD-based therapy (HR 1.38, 95%CI: 1.10-1.73) and no IMiD (HR 1.47, 95%CI: 1.01-2.13) (interaction P=0.78), PI-based therapy (HR 1.43, 95%CI: 1.04-1.97) and no PI, (HR 1.39, 95%CI: 1.09-1.76) (interaction P=0.87), and ASCT in eli- gible patients (HR 1.45, 95%CI: 0.95-2.20) and non-ASCT (HR 1.40, 95%CI: 0.88-2.25) (interaction P=0.99). A landmark analysis by maintenance start showed a median OS of 69.1 months (95%CI: 64.6-NR) and 87.8 months (95%CI: 87.8-NR) (P=0.22) in
EMD and non-EMD patients, respectively. EMD size was not cor- related with median OS: patients with EMD ≤3 cm 58.5 months (95%CI: 38.4-NR), patients with EMD >3 cm 63.7 months (95%CI: 48.2-NR), and patients without EMD 79.9 months (95%CI: 75.8-88.3) (Figure 4). The same analysis was done with the EMD size threshold at 5 cm (Online Supplementary Figure S6). Median OS according to EMD number was as follows: single EMD localization 70.1 months (95%CI: 50.4-NR), multiple EMD localizations 45 months (95%CI: 38.2-NR), and no EMD 79.9 months (95%CI: 75.8-88.3), single EMD versus no EMD (HR 1.33, 95%CI: 1.07-1.67; P=0.01), and multiple EMD localizations versus no EMD (HR 1.62, 95%CI: 1.11-2.38; P=0.01). Median OS was not correlated with EMD site: PO 67.3 months (95%CI: 50.4-NR), EMP 70.1 months (95%CI: 16.9-NR), and no EMD 79.9 months (95%CI: 75.8-88.3), PO versus no EMD (HR 1.39, 95%CI: 1.13- 1.70; P=0.001), and EMP versus no EMD (HR 1.24, 95%CI: 0.55- 2.78; P=0.60) (Figure 1B).
Discussion
To the best of our knowledge, this is the first meta- analysis of MM clinical trials focusing on patients with EMD so far reported. We included eight Fonesa Onlus and
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Figure 1. (A) Progression-free survival (PFS) and (B) overall survival (OS) according to extramedullary disease presence and type. EMD: extramedullary disease; EMP: extramedullary plasmocytoma; PO: paraosseous plasmocytoma.
Figure 2. Progression-free survival (PFS) according to extramedullary disease features. (A) PFS according to extramedullary disease (EMD) presence and size. (B) PFS according to single or multiple EMD localizations.
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