title: Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study.
abstract: BACKGROUND
  We previously showed that consolidation therapy with thalidomide and prednisolone improved progression-free and overall survival in patients with multiple myeloma who had undergone autologous stem-cell transplantation. We aimed to assess whether these survival advantages were durable at 5 years.
  
  
  METHODS
  The ALLG MM6 trial was a multicentre, open-label, randomised phase 3 trial done between Jan 13, 2002, and March 15, 2005, at 29 sites in Australia and New Zealand. Patients with newly diagnosed multiple myeloma were randomly assigned (1:1), via computer-generated randomisation charts, to receive indefinite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratified by treating centre and pre-transplantation concentrations of β2 microglobulin. Patients and treating physicians were not masked to treatment allocation. Primary endpoints were progression-free survival and overall survival. Analysis was by intention to treat. Secondary endpoints were overall response to salvage therapy, incidence of second primary malignancy incidence, and cost-effectiveness. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12607000382471.
  
  
  RESULTS
  We randomly assigned 269 patients to the thalidomide (n=114) or control group (n=129). After a median follow-up of 5·4 years (IQR 3·1-7·2), estimated 5-year progression-free survival was 27% (95% CI 23-32) in the thalidomide group and 15% (11-18) in the control group (hazard ratio [HR] 0·16, 95% CI 0·044-0·58; p=0·0054) and 5-year overall survival was 66% (95% CI 61-70) and 47% (42-51), respectively (HR 0·12, 95% CI 0·028-0·56; p=0·0072). There was no difference in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-effectiveness ratio was AUS$26 996 per mean life-year gained.
  
  
  CONCLUSIONS
  Consolidation therapy with thalidomide and prednisolone after autologous stem-cell transplantaion is an acceptable therapeutic approach when alternative drugs are not available.
  
  
  BACKGROUND
  Pharmion Corporation, Novartis Pharmaceuticals, Amgen Australia, The Merrin Foundation, and Alfred Health.
authors.affiliation: Alfred Health-Monash University, Melbourne, VIC, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Kalff
authors.affiliation: Alfred Health-Monash University, Melbourne, VIC, Australia.
authors.forename: Nola
authors.initials: N
authors.lastname: Kennedy
authors.affiliation: Alfred Health-Monash University, Melbourne, VIC, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Smiley
authors.affiliation: Peter MacCallum Cancer Institute, Melbourne, VIC, Australia; University of Melbourne, Parkville, VIC, Australia.
authors.forename: H Miles
authors.initials: HM
authors.lastname: Prince
authors.affiliation: Royal Melbourne Hospital, Parkville, VIC, Australia; University of Melbourne, Parkville, VIC, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roberts
authors.affiliation: Westmead Hospital, Sydney, NSW, Australia.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Bradstock
authors.affiliation: Centre for Health Economics Research and Evaluation, University of Technology, Sydney, NSW, Australia.
authors.forename: Richard
authors.initials: R
authors.lastname: De Abreu Lourenço
authors.affiliation: University of Otago, Christchurch, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Frampton
authors.affiliation: Alfred Health-Monash University, Melbourne, VIC, Australia. Electronic address: andrew.spencer@monash.edu.au.
authors.forename: Andrew
authors.initials: A
authors.lastname: Spencer