Since 2000 — after years in which dexamethasone and melphalan was standard treatment — clinicians now have numerous options for patients with relapsed and/or refractory multiple myeloma (R/R MM). These include the immunomodulatory agent, thalidomide, as well as bortezomib, the first proteasome inhibitor introduced in 2004, and 8 other treatments: lenalidomide, pomalidomide, carfilzomib, ixazomib, vorinostat, panobinostat, elotuzumab, and daratumumab.

Yet as the authors of a systematic literature review and network meta-analysis of treatment outcomes noted, “direct comparisons of these novel treatments…are lacking.”1

Chrissy H.Y. van Beurden-Tan, MSc, of the Erasmus Medical Center in Rotterdam, the Netherlands, who was one of the authors of the review, wrote that “bortezomib and lenalidomide were almost simultaneously introduced; both were compared with the former standard treatment, dexamethasone. There is no direct evidence demonstrating whether bortezomib or lenalidomide is superior because no head-to-head comparison has been made. As a consequence, all subsequent treatments were compared with either bortezomib or lenalidomide (with or without dexamethasone). This resulted in a lack of direct comparison among different treatment classes….”

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A systematic literature review identified 17 phase 3 randomized controlled trials including 18 treatment options. A network meta-analysis to evaluate the relative efficacy of each treatment found that the “best treatment” for prolonging progression-free survival (PFS) was daratumumab/lenalidomide/dexamethasone, with a hazard ratio (HR) 0.13 vs an HR of 1 for dexamethasone.

Thirteen other combinations had HRs ranging from 0.24 (carfilzomib/lenalidomide/dexamethasone) to 0.76 (thalidomide/dexamethasone). All 3 best treatment options were triple-combination regimens in combination with lenalidomide/dexamethasone, with doublet regimens ranking “at the bottom of the list.”

The authors cautioned that data on adverse-event profiles and quality of life were not assessed, and that overall survival HRs for most of the trials are still immature.

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These results apply to “the average patient,” they noted: “selecting the most appropriate treatment option also depends on individual patient characteristics and individual preferences. Our results, however, provide insight into the rank order of the efficacy of treatments and can help doctors to select the most appropriate treatment for each individual patient.”