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New drugs in MM with EMD
Table 1. Source studies.
Trial Code
GIMEMA-MM-05-0528 2005-004714-32
Treatment
4 PAD induction followed by 2 Mel100 intensification followed by 4 RP consolidation and R maintenance
9 VMP induction or 9 VMPT
induction followed by 2 years VT maintenance
4 Rd induction, mobilization,
6 MPR or 2 Mel200 intensification followed by R maintenance
until PD or observation
4 Rd induction, mobilization,
6 CPR or 2 Mel200 intensification followed by RP or R maintenance until PD
9 Rd or MPR or CPR induction followed by RP or R maintenance until PD
9 VP or CVP or VMP induction
followed by V maintenance until PD
DrugsMaintenance N.of Years Age Outcome Patients enrollement population PFS
Outcome Pubblication
GIMEMA-MM-03-0529
RV-MM-PI-20930
RV-MM-EMN-44131
EMN0132
MMY206933
IST-CAR-50634
NCT01063179
NCT00551928
NCT01091831
NCT01093196
NCT01190787
IMiD-PI
IMiD-PI
Yes 103
Random 511
2005-2008
2006-2009
2007-2009
2009-2011
2009-2012
2010-2012
≤75 Median PFS: 48 months
≥65 Median PFS: VMPT-VT: 35 months
VMP:
25 months <65 Median PFS:
OS
5yrs OS: 63%
5yrs OS:
VMPT-VT: 61% VMP:51%
year(s)
2010-2013
2010-2014
PI
for FDT
or observation
Random 402 for maintenance
or observation
4yrs OS: 2014 MPR:22months MPR:65%
IMiD Yes 389
IMiD Yes 654
PI Yes 152
ASCT:43months ASCT:81%
<65 Median PFS: 4yrs OS: 2015
CRD: 29 months CRD: 73% ASCT:43months ASCT:86%
≥65 Median PFS: MPR: 24 months CPR: 20 months
VCP: 15 months
4yrs OS: 2016 MPR: 65%
CPR: 68%
Rd: 58%
2yrs OS: 2016
VP: 60% VCP: 70% VMP: 76%
Rd: 21 months
≥65 Median PFS: VP: 14 months
IST-CAR-56135
NCT01346787 NCT01857115
9 KCd induction followed by K maintenance until PD 9 KCd induction followed by K maintenance until PD
PI Yes 58 PI Yes 63
2011-2012 2013-2015
VMP: 17 months
≥65 2yrsPFS:76%, 2yrsOS:87% 2014
≥65 2yrsPFS:53%, 2yrsOS:81% 2018 lated liposomal doxorubicin -dexamethasone; PD: progression disease; IMiD: immunomodulatory drug; PI: proteasome inhibitor; PFS: progression-free survival; OS: overall survival; FDT:
V: bortezomib; M: melphalan; P: prednisone; T: thalidomide; C: cyclophosphamide; K: carfilzomib; R: lenalidomide; d: dexamethasone; Mel200: high-dose melphalan; PAD: bortezomib-pegy-
fixed-duration therapy; yrs: years.
30-70%), hemoglobin 12.0 gr/L (IQ range 10.5-13.6) versus 10.7 gr/L (IQ range 9.5-12.1), median creatinine clearance 75 mL/min per 1.73 m2 (IQ range 48-98) versus 66 (IQ range 41-88), respective- ly. EMD patients had ISS I stage in 45% of cases, compared to 33% in non-EMD patients (P<0.001).
Efficacy
Progression-free survival. The median follow up was 62 months (IQ range 34-75) in EMD, and 65 months (IQ range 40-77) in non-EMD patients. Median PFS was 25.3 months (95%CI: 21.7- 28.7) and 25.2 months (95%CI: 24.2-27.0) in EMD and non-EMD patients, respectively. Five-year PFS was 19% (95%CI: 15-25%) and 22% (95%CI: 20-24%) (P=0.46) in EMD and non-EMD patients, respectively (Online Supplementary Figure S1), and there were no differences between EMP, PO, and non-EMD (Figure 1A). In multivariate analysis the presence of EMD did not impact on PFS (HR 1.15, 95%CI: 0.99-1.33; P=0.06), while other known prognostic factors retained their significance: high risk versus stan- dard cytogenetic (HR 1.35, 95%CI: 1.20-1.52; P<0.001), and ISS III versus I (HR 1.74, 95%CI: 1.53-1.98; P<0.001) (Online Supplementary Figure S2). Type of therapy had no impact on PFS:
IMiD-based therapy (HR 1.14, 95%CI: 0.96-1.35) and no IMiD (HR 1.18, 95%CI: 0.87-1.59) (interaction P=0.86), PI-based therapy (HR 1.33, 95%CI: 1.04-1.71) and no PI, (HR 1.04, 95%CI: 0.87- 1.25) (interaction P=0.12), and ASCT in eligible patients (HR 1.10, 95%CI: 0.81-1.50) and non-ASCT (HR 1.04, 95%CI: 0.73-1.47) (interaction P=0.72). A landmark analysis from maintenance start showed a median PFS of 23.4 months (95%CI: 19.1-30.1) and 23.5 months (95%CI: 21.8-25.7) (P=0.30) in EMD and non-EMD patients, respectively. EMD size was not correlated with median PFS: patients with EMD ≤3 cm 26.0 months (95%CI: 18.5-37.1), patients with EMD >3 cm 23.7 months (95%CI: 18.8-28.2), and patients without EMD 25.2 months (95%CI: 24.2-27.0) (Figure 2). The same results were observed with the EMD size threshold at 5 cm (Online Supplementary Figure S3). Median PFS according to EMD number was as follows: single EMD localization 26.1 months (95%CI: 22.5-30.1), multiple EMD localizations 19.4 months (95%CI: 14.9-33.1), and no EMD 25.2 months (95%CI: 24.2-27.0). Median PFS was not correlated with EMD site: PO 24.3 months (95%CI: 21.2-28.2), EMP 26.1 months (95%CI: 8.0-NR), and no EMD 25.2 months (95%CI: 24.2-27.0), PO versus no EMD (HR 1.14, 95%CI: 0.98-1.33; P=0.10), and EMP versus no EMD (HR
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