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H.M. Blommestein et al.
Results versus dexamethasone
Figure 3 presents the HRs with the corresponding 95%CI for
PFS and the P-score of the NMA in which dexamethasone was used as comparator for the remaining 20 “other treatment” options. HRs above 1 indicate that the “other treatment” is less effective than the comparator treatment, dexamethasone; HRs below 1 indicate that the “other treatment” is more effective than dexamethasone. All first-line NTE NDMM treatment options were better compared to the reference treatment dexamethasone (i.e. reducing the risk of progression or death compared to dexam- ethasone). HRs ranged between 0.19-0.90; however, not all treat- ments were statistically significantly different from dexametha- sone, because of wide 95%CIs. DaraVMP and VMPT-VT were identified as the most effective treatment options as they had the highest and almost similar P-scores (i.e. a 96% and 93% certainty that this treatment is better than another treatment, averaged over all competing treatments) and most favorable relative treatment effects compared to dexamethasone (i.e. HR: 0.19, 95%CI: 0.08- 0.45 and HR 0.22, 95%CI: 0.10-0.51 for DaraVMP and VMPT-VT, respectively). The HRs and 95%CIs for currently recommended treatments, VRd, VMP and Rd compared to dexamethasone, were 0.31 (95%CI: 0.16-0.59), 0.39 (95%CI: 0.20-0.75), and 0.44 (95%CI: 0.29-0.65), respectively. Selecting MPT as a reference treatment does not change the hierarchy of the treatments as the
P-score values do not change if one considers a different reference treatment. Compared to MPT, only DaraVMP had a statistically lower HR for PFS (HR 0.41, 95%CI: 0.19-0.91; P<0.05) (Online Supplementary Appendix 6).
Scenario analysis network meta-analysis
In order to rule out that grouping of MPT and MPT-T would affect the outcome of the analysis, we performed a scenario in which we grouped IFM 01/01, IFM 99/06 and Sacchi et al. 2011, as MPT and GIMEMA, HOVON49, TMSG and NMSG as MPT-T. The MPT-T group was connected in the network to the MPT-T arm from the HOVON87 trial and the ECOG E1A06 trial. Overall, the results were comparable to the base case (Online Supplementary Appendix 7). We found similar results for MPT (HR 0.46, 95%CI: 0.30-0.71) and MPT-T (HR 0.47, 95% CI 0.30-0.73) compared to D.
The second scenario, based on the trials included by Weisel et al.,12 showed lower HRs for PFS for Rd compared to VMP, MPT and MP, but the 95%CI for VMP overlapped with Rd [Rd vs. VMP: HR 0.73, 95%CI: 0.48-1.11 (Online Supplementary Appendix 8)].
Results from the third scenario analysis (fixed effect model instead of random effects model) are presented in Online Supplementary Appendix 9. While the HRs from the fixed effect model are quite similar, the 95%CIs are smaller, as is typical for fixed effect models.
Figure 3. Results of the network meta-analysis in which dexamethasone was used as comparator. HR: hazard ratio; CI: confidence interval. For abbreviations for treatments, see Figure 2.
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