Response to treatment

In the three included trials, the response rates of previous treatment after ASCT have been reported for all participants, and no significant difference was found between experimental groups and control groups (P=0.12). As shown in Figure 2A, the Egger’s regression plot (intercept P-value =0.0383<0.05) indicated publication bias (Figure S1). Hence, we used the “trim and fill” method to fill one hypothetical (missing) study to the primary meta-analysis to make it unbiased. After filling, intercept P-value of Egger’s regression was 0.4804>0.05 (Figure S1). The adjusted pooled OR for overall response rate (CR/nCR+VGPR+PR) was 1.85 (95% CI: 1.29–2.64), and the pooled ORs for consolidation and maintenance therapy studies were 1.63 (95% CI: 0.81–3.82) and 1.93 (95% CI: 1.28–2.92), respectively. Moreover, from the cumulative forest plot, OR has an increasing trend as consolidation studies are added. Pooled OR from cumulative analysis of consolidation therapy was 1.63 (95% CI: 0.81–3.82), and no significant difference was found. After adding the maintenance treatment study conducted by Pieter Sonneveld, the OR was larger than 1 (OR =1.85, 95% CI: 1.29–2.64). On the other hand, our integrate analysis demonstrated that the rate of CR/nCR in bortezomib-based groups was significantly higher than that in non-bortezomib-based groups (53.0% vs 39.8%,P<0.001), and the pooled OR for the rates of CR/nCR was 1.75 (95% CI: 1.42–2.15, Figures 2B, S2), and the pooled ORs for consolidation and maintenance therapy studies were 1.62 (95% CI: 1.18–2.22) and 1.86 (95% CI: 1.40–2.46), respectively. Meanwhile, the cumulative meta-analysis indicated that the beneficial effect of bortezomib-based post-transplantation treatment was more obvious when it was administrated as maintenance treatment with more narrow confidence interval (OR =1.75, 95% CI: 1.42–2.15 vs OR =1.62, 95% CI: 1.18–2.22).


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(To view a larger version of Figure 2, click here.)

Progression-free survival

All the included three trials reported PFS, and the pooled HR for PFS shown in Figure 3A was 0.73 (95% CI: 0.67–0.81), indicating that there was a 27% reduction in the risk of disease progression or death with bortezomib-based therapy after ASCT. No publication bias was detected (Egger’s regression intercept P-value =0.6994>0.05, Figure S3). Moreover, the pooled ORs for consolidation and maintenance therapy studies were 0.73 (95% CI: 0.65–0.81) and 0.75 (95% CI: 0.63–0.90), respectively. Meanwhile, pooled HR from the cumulative meta-analysis for PFS confirmed the beneficial effect of bortezomib-based over non-bortezomib-based post-transplantation therapy.

(To view a larger version of Figure 3, click here.)