Triplet regimens combining immunomodulatory drugs and proteasome inhibitors are the most effective frontline therapeutic approaches among patients with transplant-eligible multiple myeloma (MM), according to a study published in Hematological Oncology.1

Autologous transplantation, preceded by frontline induction therapy, is the current standard of care for younger, fit patients with MM. Evidence suggests that the success of frontline induction therapies affects post-transplant results, but because of the rapid development of various agents, there is a paucity of comparative or efficacy data on these novel agents when they are administered in  combination. 

For this systematic review and mixed-treatment comparison meta-analysis, researchers evaluated the outcomes of 21 clinical studies encompassing 6474 newly diagnosed, transplant-eligible patients with MM and 11 unique frontline induction regimens. 

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Overall survival (OS) analyses revealed that the CRD (cyclophosphamide, lenalidomide, dexamethasone) regimen was superior compared with TD-based (thalidomide, dexamethasone, with or without cyclophosphamide; hazard ratio [HR], 0.76), VAD-based (mainly doxorubicin, dexamethasone, vincristine, and variants including cyclophosphamide and/or etoposide; HR, 0.71), and Z-Dex (idarubicin, dexamethasone; HR, 0.37) regimens.

Progression-free survival (PFS) analyses showed that the VTD (bortezomib, thalidomide, dexamethasone) regimen was superior to TD-based regimens (HR, 0.66), VAD-based regimens (HR, 0.61), Z-Dex (HR, 0.42), and high-dose dexamethasone (HR, 0.62). 

Bortezomib/thalidomide regimens were found to not be superior to lenalidomide. 

The VTD regimen led to the highest overall and complete response rates compared with the other protocols, and demonstrated superiority over regimens that contained thalidomide alone. 

The authors concluded that “further studies comparing directly these treatment approaches (together with pipeline drugs), should be able to establish the role of even newer agents on frontline therapy framework and clarify optimal sequence of protocols to be applied on conventional practice.”


  1. Sekine L, Ziegelmann PK, Manica D, et al. Frontline treatment for transplant-eligible multiple myeloma: a 6,474 patients network meta-analysis[published online August 20, 2018]. Hematol Oncol. doi: 10.1002/hon.2552