MP versus MPT for previously untreated elderly patients with multiple myeloma

A meta-analysis of 1685 individual-patient data from six randomized clinical trials.

Peter Fayers, Antonio Palumbo, Cyrille Hulin, Anders Waage, Pierre Wijermans, Meral Beksac, Sara Bringhen, Jean Yves Mary, Peter Gimsing, Fabian Termorshuizen, Rauf Haznedar, Tommaso Caravita, Philippe Moreau, Ingemar Turesson, Pellegrino Musto, Lofti Benboubke, Martijn Schaafsma, Pieter Sonneveld, Thierry Facon

Research output: Contribution to journalArticle

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Abstract

The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%.
Original languageEnglish
Pages (from-to)1239-1247
Number of pages9
JournalBlood
Volume118
Issue number5
Early online date4 Aug 2011
DOIs
Publication statusPublished - 4 Aug 2011

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Thalidomide
Multiple Myeloma
Meta-Analysis
Randomized Controlled Trials
Survival
Disease-Free Survival
Hazards
Confidence Intervals
Melphalan
Prednisone

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MP versus MPT for previously untreated elderly patients with multiple myeloma : A meta-analysis of 1685 individual-patient data from six randomized clinical trials. / Fayers, Peter; Palumbo, Antonio; Hulin, Cyrille; Waage, Anders; Wijermans, Pierre; Beksac, Meral; Bringhen, Sara; Mary, Jean Yves; Gimsing, Peter; Termorshuizen, Fabian; Haznedar, Rauf; Caravita, Tommaso; Moreau, Philippe; Turesson, Ingemar; Musto, Pellegrino; Benboubke, Lofti; Schaafsma, Martijn; Sonneveld, Pieter; Facon, Thierry.

In: Blood, Vol. 118, No. 5, 04.08.2011, p. 1239-1247.

Research output: Contribution to journalArticle

Fayers, P, Palumbo, A, Hulin, C, Waage, A, Wijermans, P, Beksac, M, Bringhen, S, Mary, JY, Gimsing, P, Termorshuizen, F, Haznedar, R, Caravita, T, Moreau, P, Turesson, I, Musto, P, Benboubke, L, Schaafsma, M, Sonneveld, P & Facon, T 2011, 'MP versus MPT for previously untreated elderly patients with multiple myeloma: A meta-analysis of 1685 individual-patient data from six randomized clinical trials.', Blood, vol. 118, no. 5, pp. 1239-1247. https://doi.org/10.1182/blood-2011-03-341669
Fayers, Peter ; Palumbo, Antonio ; Hulin, Cyrille ; Waage, Anders ; Wijermans, Pierre ; Beksac, Meral ; Bringhen, Sara ; Mary, Jean Yves ; Gimsing, Peter ; Termorshuizen, Fabian ; Haznedar, Rauf ; Caravita, Tommaso ; Moreau, Philippe ; Turesson, Ingemar ; Musto, Pellegrino ; Benboubke, Lofti ; Schaafsma, Martijn ; Sonneveld, Pieter ; Facon, Thierry. / MP versus MPT for previously untreated elderly patients with multiple myeloma : A meta-analysis of 1685 individual-patient data from six randomized clinical trials. In: Blood. 2011 ; Vol. 118, No. 5. pp. 1239-1247.
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abstract = "The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95{\%} confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95{\%} confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59{\%} on MPT and 37{\%} on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20{\%}.",
author = "Peter Fayers and Antonio Palumbo and Cyrille Hulin and Anders Waage and Pierre Wijermans and Meral Beksac and Sara Bringhen and Mary, {Jean Yves} and Peter Gimsing and Fabian Termorshuizen and Rauf Haznedar and Tommaso Caravita and Philippe Moreau and Ingemar Turesson and Pellegrino Musto and Lofti Benboubke and Martijn Schaafsma and Pieter Sonneveld and Thierry Facon",
note = "Authorship Contribution: P.M.F. was responsible for the data analysis and wrote the manuscript; and all authors were the principal investigators and major contributors or statisticians for respective trials, participated in the elaboration of the meta-analysis statistical plan, and made important contribution to the preparation and revision of the manuscript. Conflict-of-interest disclosure: A.P. has honoraria and an advisory role for Celgene. S.B. has honoraria from Celgene. C.H., P. Moreau, and T.F. have honoraria or an advisory role for Celgene, Pharmion, and Janssen Cilag. A.W. and P.G. have an advisory role for Janssen Cilag, Celgene, and Mundipharma. M.B. has honoraria from and is a member of the Speakers Bureau for Celgene and Ortho Biotech. The remaining authors declare no competing financial interests",
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T1 - MP versus MPT for previously untreated elderly patients with multiple myeloma

T2 - A meta-analysis of 1685 individual-patient data from six randomized clinical trials.

AU - Fayers, Peter

AU - Palumbo, Antonio

AU - Hulin, Cyrille

AU - Waage, Anders

AU - Wijermans, Pierre

AU - Beksac, Meral

AU - Bringhen, Sara

AU - Mary, Jean Yves

AU - Gimsing, Peter

AU - Termorshuizen, Fabian

AU - Haznedar, Rauf

AU - Caravita, Tommaso

AU - Moreau, Philippe

AU - Turesson, Ingemar

AU - Musto, Pellegrino

AU - Benboubke, Lofti

AU - Schaafsma, Martijn

AU - Sonneveld, Pieter

AU - Facon, Thierry

N1 - Authorship Contribution: P.M.F. was responsible for the data analysis and wrote the manuscript; and all authors were the principal investigators and major contributors or statisticians for respective trials, participated in the elaboration of the meta-analysis statistical plan, and made important contribution to the preparation and revision of the manuscript. Conflict-of-interest disclosure: A.P. has honoraria and an advisory role for Celgene. S.B. has honoraria from Celgene. C.H., P. Moreau, and T.F. have honoraria or an advisory role for Celgene, Pharmion, and Janssen Cilag. A.W. and P.G. have an advisory role for Janssen Cilag, Celgene, and Mundipharma. M.B. has honoraria from and is a member of the Speakers Bureau for Celgene and Ortho Biotech. The remaining authors declare no competing financial interests

PY - 2011/8/4

Y1 - 2011/8/4

N2 - The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%.

AB - The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%.

U2 - 10.1182/blood-2011-03-341669

DO - 10.1182/blood-2011-03-341669

M3 - Article

VL - 118

SP - 1239

EP - 1247

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -