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

Research output: Contribution to journalArticleResearchpeer-review

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 indefi nite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratifi ed by treating centre and pre-transplantation concentrations of ß2 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-eff ectiveness. 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 followup 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 diff erence in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-eff ectiveness 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.

Original languageEnglish
Pages (from-to)e112-e119
Number of pages8
JournalThe Lancet Haematology
Volume1
Issue number3
DOIs
Publication statusPublished - 2014

Cite this

@article{3ea91d0cd97f41099b42035723983f51,
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 indefi nite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratifi ed by treating centre and pre-transplantation concentrations of {\ss}2 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-eff ectiveness. 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 followup 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 diff erence in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-eff ectiveness 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.",
author = "Anna Kalff and Nola Kennedy and Angela Smiley and {Miles Prince}, H. and Roberts, {Andrew W} and Kenneth Bradstock and {de Abreu Louren{\cc}o}, Richard and Chris Frampton and Andrew Spencer",
year = "2014",
doi = "10.1016/S2352-3026(14)00022-2",
language = "English",
volume = "1",
pages = "e112--e119",
journal = "The Lancet Haematology",
issn = "2352-3026",
publisher = "Elsevier",
number = "3",

}

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

In: The Lancet Haematology, Vol. 1, No. 3, 2014, p. e112-e119.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Thalidomide and prednisolone versus prednisolone alone as consolidation therapy after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma

T2 - Final analysis of the ALLG MM6 multicentre, open-label, randomised phase 3 study

AU - Kalff, Anna

AU - Kennedy, Nola

AU - Smiley, Angela

AU - Miles Prince, H.

AU - Roberts, Andrew W

AU - Bradstock, Kenneth

AU - de Abreu Lourenço, Richard

AU - Frampton, Chris

AU - Spencer, Andrew

PY - 2014

Y1 - 2014

N2 - 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 indefi nite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratifi ed by treating centre and pre-transplantation concentrations of ß2 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-eff ectiveness. 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 followup 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 diff erence in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-eff ectiveness 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.

AB - 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 indefi nite prednisolone maintenance alone (control group) or in combination with 12 months of thalidomide consolidation (thalidomide group) after autologous stem-cell transplantation. Randomisation was stratifi ed by treating centre and pre-transplantation concentrations of ß2 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-eff ectiveness. 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 followup 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 diff erence in overall response to salvage therapy, survival post-progression, or incidence of secondary malignancies between the two groups. Incremental cost-eff ectiveness 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.

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U2 - 10.1016/S2352-3026(14)00022-2

DO - 10.1016/S2352-3026(14)00022-2

M3 - Article

VL - 1

SP - e112-e119

JO - The Lancet Haematology

JF - The Lancet Haematology

SN - 2352-3026

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ER -