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).

8000Background: The role of upfront ASCT for newly diagnosed (ND) MM (NDMM) patients (pts) has been questioned in the novel agent era. Methods: 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. Results: From February 2011 through April 2014, 1503 pts aged ≤65 years with symptomatic NDMM were registered. Of these, 1308 pts were eligible for R1 and 1266 who were randomized (1:1 ratio; stratification by ISS stage) to VMP (512 pts) or HDM (1±2 ASCT) (754 pts) were analyzed. Median follow up from R1 was 24 months. PFS was significantly prolonged in pts randomized to HDM (HR=0.76; 95% CI=0.61-0.94; P=0.010), a benefit retained across predefined pt subgroups, including those with revised ISS stage III (HR=0.52; CI=0.32-0.84; P=0.008) and high-risk cytogenetics [t(4;14) ± del(17p) ± del(1p) ± 1q gain] (HR=0.72; CI=0.54-0.97; P=0.028). Superior rate of ≥ very good partial response was observed with HDM (84%) vs VMP (74%) (odds ratio=1.90; CI=1.42-2.54; P