Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma

Results of a randomized comparison with vincristine, doxorubicin, and dexamethasone


  • The following regional coordinators were responsible for the study: L. Ahlberg (Linkoping University Hospital, Linkoping, Sweden); K. Carlsson (Akademiska Hospital, Uppsala, Sweden); I. M. S. Dahl (Tromso University Hospital, Tromso, Norway); K. Forsberg (Umea University Hospital, Umea, Sweden); T. Gedde-Dahl (Rikshospitalet, Oslo, Norway); P. Gimsing (Rigshospitalet, Copenhagen, Denmark); J. Hammerstrom (St. Olav Hospital, Trondheim, Norway); H. E. Johnsen (Herlev Hospital, Herlev, Denmark); S. Lenhoff (Lund University Hospital, Lund, Sweden); O. Linder (Orebro University Hospital, Orebro, Sweden); U.-H. Mellqvist (Sahlgrenska University Hospital, Gothenburg, Sweden); I. Nesthus (Haukeland Hospital, Bergen, Norway); J. Lang Nielsen (Aarhus University Hospital, Aarhus, Denmark); and J. M. Tangen (Ulleval University Hospital, Oslo, Norway).



Today, intensive therapy that includes high-dose melphalan with autologous stem cell transplantation (ASCT) is considered standard therapy in younger patients with newly diagnosed myeloma. When the current trial was initiated, combined vincristine, doxorubicin, and dexamethasone (VAD) was the most commonly used induction therapy before ASCT and yielded rapid major responses without interfering with stem cell harvest. However, the administration of VAD demands a central venous access, and well-described toxicities are associated with the therapy. This randomized trial, which was initiated in 2001 by the Nordic Myeloma Study Group, was an attempt to bring a larger portion of patients to ASCT more quickly.


Patients were randomized to receive either 3 cycles of VAD or 2 courses of cyclophosphamide plus dexamethasone (Cy-Dex) (cyclophosphamide at a dose of 1000 mg/m2 on Day 1 and dexamethasone at a dose of 40 mg per day on Days 1–4 and 9–12, repeated on Day 22) as initial therapy followed by stem cell mobilization, harvest, and finally ASCT.


No significant difference was observed in the proportion of patients undergoing ASCT (VAD [86%] vs Cy-Dex [87%]). During the first 4 months after the initiation of therapy, the mortality rates were 5.8% for VAD and 1.9% for Cy-Dex (P = .08). The response rates after ASCT were comparable (partial response or better: VAD: 80% vs Cy-Dex: 81%). In both groups, the median event-free survival was 29 months, and the overall survival rate at 3 years was 75%.


The current results indicated that Cy-Dex before ASCT has efficacy comparable to that of VAD. It also demonstrated that a short course of alkylator therapy using cyclophosphamide does not affect stem cell harvest or transplantation. Cancer 2008. © 2007 American Cancer Society.