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

Anna Kalff; Nola Kennedy; Angela Smiley; H Miles Prince; Andrew W Roberts; Kenneth Bradstock; Richard De Abreu Lourenço; Chris Frampton; Andrew Spencer

doi:10.1016/S2352-3026(14)00022-2

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

Lancet Haematol. 2014 Dec;1(3):e112-9. doi: 10.1016/S2352-3026(14)00022-2. Epub 2014 Dec 1.

Authors

Anna Kalff¹, Nola Kennedy¹, Angela Smiley¹, H Miles Prince², Andrew W Roberts³, Kenneth Bradstock⁴, Richard De Abreu Lourenço⁵, Chris Frampton⁶, Andrew Spencer⁷

Affiliations

¹ Alfred Health-Monash University, Melbourne, VIC, Australia.
² Peter MacCallum Cancer Institute, Melbourne, VIC, Australia; University of Melbourne, Parkville, VIC, Australia.
³ Royal Melbourne Hospital, Parkville, VIC, Australia; University of Melbourne, Parkville, VIC, Australia.
⁴ Westmead Hospital, Sydney, NSW, Australia.
⁵ Centre for Health Economics Research and Evaluation, University of Technology, Sydney, NSW, Australia.
⁶ University of Otago, Christchurch, New Zealand.
⁷ Alfred Health-Monash University, Melbourne, VIC, Australia. Electronic address: andrew.spencer@monash.edu.au.

PMID: 27029229
DOI: 10.1016/S2352-3026(14)00022-2

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.

Findings: 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.

Interpretation: Consolidation therapy with thalidomide and prednisolone after autologous stem-cell transplantaion is an acceptable therapeutic approach when alternative drugs are not available.

Funding: Pharmion Corporation, Novartis Pharmaceuticals, Amgen Australia, The Merrin Foundation, and Alfred Health.