Upfront autologous stem cell transplantation (ASCT) versus novel agent-based therapy for multiple myeloma (MM): A randomized phase 3 study of the European Myeloma Network (EMN02/HO95 MM trial)

Abstract

Background: The role of upfront ASCT for newly diagnosed (ND) MM (NDMM) patients (pts) has been questioned in the novel agent era. Method(s): A phase 3 study was designed to compare [random (R) 1] 4 cycles of bortezomib-melphalan-prednisone (VMP) vs high- dose melphalan (HDM) and single or double ASCT (this latter limited to centers applying a tandem ASCT policy) as intensification therapy following induction with bortezomib- cyclophosphamide-dexamethasone and subsequent collection of peripheral blood stem cells. Consolidation therapy with bortezomib-lenalidomide-dexamethasone vs no consolidation (R2) was planned after VMP and HDM, followed by lenalidomide maintenance until progression or toxicity in both treatment arms. Primary study end point was progression-free survival (PFS) from R1. A first prespecified interim analysis was performed in January 2016 when at least 33% of the required events had been observed. Results are herein reported. Result(s): From February 2011 through April 2014, 1503 pts aged = very good partial response was observed with HDM (84%) vs VMP (74%) (odds ratio=1.90; CI=1.42-2.54; P<0.0001). In a Cox regression analysis, randomization to HDM (HR=0.61, CI=0.45-0.82; P=0.001) was confirmed to be an independent predictor of prolonged PFS. Overall survival was not yet mature and no difference between the treatment groups was evident. Conclusion(s): Upfront ASCT still remains the preferred treatment for younger NDMM pts. Further follow-up of the study is needed.