PF605 SYSTEMATIC LITERATURE REVIEW AND NETWORK‐META ANALYSIS COMPARING INDUCTION TREATMENTS FOR NEWLY DIAGNOSED MULTIPLE MYELOMA IN THE TRANSPLANT ELIGIBLE SETTING
Authors: Ashcroft J. , Patterson‐Lomba O. , Ayyagari R. , Pocoski J. , Dhanasiri S. , Roussel M. 
Published: June 2019

Background:

Use of induction regimens containing immunomodulatory drugs and proteasome inhibitors have improved overall response rates (ORRs) and overall survival (OS) in transplant‐eligible (TE) patients with newly diagnosed multiple myeloma (NDMM). However, the relative efficacy of various induction regimens is unknown due to the paucity of head‐to‐head trials. In the absence of direct evidence, indirect comparisons can be used to evaluate the relative efficacy and safety of available therapies.

Aims:

To assess the relative efficacy and safety of induction regimens currently recommended in clinical guidelines for TE patients with NDMM, with emphasis on the most commonly used regimens: lenalidomide, bortezomib + dexamethasone (RVd); bortezomib, thalidomide + dexamethasone (VTd); and bortezomib, cyclophosphamide + dexamethasone (VCd).

Methods:

A systematic literature review of MEDLINE, EMBASE, Cochrane Library, and key conferences was performed to identify randomized clinical trials (RCTs) satisfying the following criteria: (a) included adult TE patients with NDMM, (b) included ≥2 induction regimens recommended in current clinical guidelines, and (c) reported survival, response, or safety outcomes. Pairwise risk ratios (RRs), their corresponding 95% credible intervals, and relative treatment rankings were obtained via a Bayesian network meta‐analysis (NMA).

Results:

Seven trials were identified. For very good partial response or better (≥VGPR), 4 trials and 6 interventions (bortezomib + dexamethasone [Vd], RVd, VTd, VCd, VCd + lenalidomide [VCRd], and bortezomib + doxorubicin + dexamethasone [PAd]) were eligible. VCRd and RVd were associated with higher ≥VGPR rates than the other regimens (Table). For ORR, 5 trials and 7 interventions (Vd, RVd, VTd, VCd, VCRd, PAd, and lenalidomide + dexamethasone [Rd]) were eligible. VCRd, VTd, and RVd had similar ORRs and were numerically superior to the other regimens (median RRs for RVd, VCRd, and VCd vs VTd were 0.96, 1.00, and 0.88, respectively). For rates of grade ≥3 adverse events (AEs), 4 trials and 6 interventions (Vd, RVd, VTd, VCd, VCRd, and PAd) were eligible. The doublet Vd had the lowest AE rate (RR vs VTd was 0.89), whereas triplet regimens had similar AE rates (median RRs for RVd and PAd vs VTd were 1.00 and 1.03, respectively).

Summary/Conclusion:

This NMA indicates that RVd and VCRd have the most favorable benefit–risk profile, with RVd having a numerically lower AE rate than VCRd. The findings are aligned with results from a prior integrated analysis that showed that RVd has a favorable benefit–risk profile compared with VTd as induction therapy in TE NDMM patients (Rosiñol Dachs et al. Blood. 2018;132:abstract 126). Of relevance, these findings also align with data from a meta‐analysis of RCTs looking at lenalidomide maintenance following autologous stem cell transplantation, which revealed a significant OS benefit and confirmed the progression‐free survival benefits on survival outcomes (McCarthy et al. J Clin Oncol. 2017;35:3279–89). This conclusion is further strengthened by health‐related quality of life (HRQoL) data from the IFM/DFCI 2009 trial, which indicated that most HRQoL domains that were impaired at the time of diagnosis significantly improved during treatment with RVd (Roussel et al. Blood. 2018;132:abstract 716). Among the identified regimens, RVd and VCRd were associated with the highest rates of ≥VGPR, with ORR and AE rates that were comparable with the other regimens.

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