Numerous new treatment options have become available for relapsed/refractory multiple myeloma (RRMM) after a long period in which dexamethasone has been the only treatment option. However, there have been few direct comparisons, which makes it difficult to evaluate the incremental value of each new regimen. This meta-analysis sought to synthesize all efficacy evidence enabling a comparison of all treatments.
European researchers performed a systematic literature review to identify and evaluate all publicly available phase 3 randomized controlled trials (RCTs). Additionally, 2 abstracts from international hematology congresses were included to provide the most up-to-date information possible. A conventional network meta-analysis based on progression-free survival outcomes allowed a comparison of all available treatment options. Network meta-analyses are used to provide a complete overview of a treatment’s relative efficacy when head-to-head comparisons are not available. The oldest treatment, dexamethasone, was used as reference treatment.
Researchers identified 17 RCTs, including 16 treatment options: dexamethasone (Dex), oblimersen-dexamethasone (OblDex), thalidomide/thalidomide-dexamethasone (Thal/ThalDex), bortezomib/bortezomib-dexamethasone (Bor/BorDex), lenalidomide-dexamethasone (LenDex), pegylated doxorubicin-bortezomib (PeglDoxBor), bortezomib-thalidomide-dexamethasone (BorThalDex), vorinostat-bortezomib (VorinoBor), panobinostat-bortezomib-dexamethasone (PanoBorDex), carfilzomib-lenalidomide-dexamethasone (CarLenDex), pomalidomide-dexamethasone (PomDex), elotuzumab-lenalidomide-dexamethasone (EloLenDex), carfilzomib-dexamethasone (CarDex), ixazomib-lenalidomide-dexamethasone (IxaLenDex), daratumumab-lenalidomide-dexamethasone (DaraLenDex), and daratumumab-bortezomib-dexamethasone (DaraBorDex).
Researchers identified DaraLenDex as the best treatment because it had the most favorable hazard ratio (HR) of all the treatment options (0.13; 95% CrI, 0.09-0.19) and because it had the highest probability of being best (99%) in the Bayesian fixed effect modeling simulations. DaraLenDex reduced the risk of progression or death in 87% of simulations versus Dex, 80% versus Bor/BorDex, and 63% versus LenDex. LenDex performed better than Bor/BorDex in ranking (7th vs 13th) as well as in HR (0.53; 95% CrI, 0.39-0.71). Notably, lenalidomide was a component of 4 of the top 5–ranked regimens. Fourteen of 16 treatments were significantly better than Dex (HRs ranged from 0.13 to 0.76), and 11 treatments reduced the risk of progression or death with more than 50%.
When compared with other treatment regimens for RRMM, this meta-analysis identified DaraLenDex as the most effective option. As more data on newer agents become available, meta-analyses may take on an increasingly important role for payers and other healthcare decision makers, particularly if limited head-to-head studies have been conducted.
Van-Beurden-Tan CHY, et al. ASH 2016. Abstract 2144.