Single versus tandem high-dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long-term results from the phase III GMMG-HD2 trial

The prospective, randomized phase III trial GMMG-HD2 aimed at demonstrating non-inferiority of single (Arm A) versus tandem (Arm B) high-dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2-year event-free survival (EFS) in newly-diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention-to-treat population, (ITT), single/tandem HDM/ASCT: n=177/181]. After a median follow-up of more than 11years, non-inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non-inferiority threshold of 15% of the 2-year EFS rate. Neither EFS (P=053) nor overall survival (OS) (P=033) differences were observed in the ITT population. In the tandem arm, 26% (n=47/181) of patients refused a second HDM/ASCT due to non-medical reasons. A per-protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n=156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n=22/181), did not yield differences in EFS (P=061) or OS (P=016). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P=004). Ten-year OS for the entire ITT was 34% (95% confidence interval: 29-40%). OS after first relapse was significantly shortened in the tandem arm (P=004). In this study single HDM/ASCT was non-inferior to tandem HDM/ASCT in MM.