Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation

Decision making for not transplant eligible patients with multiple myeloma is complicated by lacking head-to-head comparisons of standards of care, increasing treatment modalities and rapidly evolving promising results of studies with novel regimens. To support evidence-based decision making, we performed a network meta-analysis for not transplant-eligible multiple myeloma patients that synthesizes direct and indirect evidence and enable a comparison of all treatments. Relevant randomized clinical trials were identified by a systematic literature review in EMBASE®, MEDLINE®, MEDLINE®-in-Process and the Cochrane Central Register of Controlled Trials for January-1999 to March-2016. Efficacy outcomes (i.e. the hazard ratio and 95% confidence interval for progression-free survival) were extracted and synthesized in a random effects network-meta analysis. In total 24 studies were identified including 21 treatments. According to the network-meta analysis, the hazard ratio for progression-free survival was favorable for all not transplant-eligible myeloma treatments compared to dexamethasone (hazard ratios between 0.19-0.90). Daratumumabbortezomib-melphalan-prednisone and bortezomib-melphalan-prednisone-thalidomide with bortezomib-thalidomide maintenance were identified as the most effective treatments (hazard ratio: 0.19 (95% confidence interval 0.08-0.45) and 0.22 (95% confidence interval 0.10-0.51), respectively). The hazard ratios and 95% confidence interval for currently recommended treatments, bortezomiblenalidomide-dexamethasone, bortezomib-melphalan-prednisone, and lenalidomide-dexamethasone compared to dexamethasone, were 0.31 (0.16-0.59), 0.39 (0.20-0.75) and 0.44 (0.29-0.65), respectively. In addition to identifying the most effective treatment options, we illustrate the additional value and evidence of network meta-analysis in clinical practice. In the current treatment landscape, the results of network meta-analysis may support evidence based decisions and ultimately help to optimize treatment and outcomes of not transplant eligible multiple myeloma patients.

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