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H.M. Blommestein et al.
effects model. Heterogeneity and inconsistency were assessed by decomposing the Q statistic21,22 and quantified by the I2-sta- tistic,23 which presents the percentage of the variability in effects due to heterogeneity rather than chance.24
Results
Systematic literature review
Figure 1 presents the PRISMA flow diagram; the PRISMA checklist is presented in Online Supplementary Appendix 3. The SLR identified a total of 19,773 citations from the databases. One addi- tional recent record was included (i.e. the ALCYONE trial7). After removing duplicates, 18,752 citations remained. Based on title and abstract, 17,741 citations were excluded for further analysis. The full texts of 1011 citations were reviewed and, based on this assessment, 944 citations were excluded. In the second full text
review of the remaining 67 citations, 43 citations were excluded because these did not report the most recent results (e.g. extended follow-up results were available). After the entire assessment, 24 RCTs remained and were included for data extraction and the NMA. See Figure 1 for further details of the reasons for exclusion.
These 24 RCTs included 21 treatment options: 1) Dexamethasone (D), 2) Dexamethasone-Interferon alpha (DI), 3) Melphalan 100 (M100), 4) Melphalan-Dexamethasone (MD), 5) Melphalan-Prednisone (MP), 6) Thalidomide-Dexamethasone (TD), 7) Cyclophosphamide-Thalidomide-Dexamethasone (CTD), 8) Cyclophosphamide-Thalidomide-Dexamethasone (attenuated) [CTD(a)], 9) Melphalan-Prednisone-Thalidomide/ Melphalan-Prednisone-Thalidomide and Thalidomide mainte- nance (MPT/MPT-T), 10) Bortezomib-Dexamethasone (VD), 11) Bortezomib-Thalidomide-Dexamethasone (VTD), 12) Bortezomib-Melphalan-Prednisone (VMP), 13) Bortezomib- Thalidomide-Prednisone (VTP), 14) Bortezomib-Melphalan-
Figure 1. PRISMA 2009 flow diagram: transplant not eligible multiple myeloma (TNEMM) Phase III randomized controlled trials (RCTs). n: number. From Moher et al. 2009.52
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