Single versus tandem high‐dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long‐term results from the phase III GMMG ‐ HD 2 trial

The prospective, randomized phase III trial GMMG ‐ HD 2 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 11 years, 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 = 0·53) nor overall survival ( OS ) ( P = 0·33) 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 = 0·61) or OS ( P = 0·16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM / ASCT (both P = 0·04). 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 = 0·04). In this study single HDM / ASCT was non‐inferior to tandem HDM / ASCT in MM .