Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: A meta-analysis

P. Kapoor; S. V. Rajkumar; A. Dispenzieri; M. A. Gertz; M. Q. Lacy; D. Dingli; J. R. Mikhael; V. Roy; R. A. Kyle; P. R. Greipp; S. Kumar; S. J. Mandrekar

doi:10.1038/leu.2010.313

Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: A meta-analysis

P. Kapoor, S. V. Rajkumar, A. Dispenzieri, M. A. Gertz, M. Q. Lacy, D. Dingli, J. R. Mikhael, V. Roy, R. A. Kyle, P. R. Greipp, S. Kumar, S. J. Mandrekar

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Abstract

Trials comparing efficacy of melphalan prednisone (MP) with MP plus thalidomide in transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. Although there is agreement regarding improved response rates (RRs) and higher toxicity with the addition of thalidomide to MP, the impact on progression free survival (PFS) and overall survival (OS) is less clear. We performed a meta-analysis comparing efficacy of melphalan, prednisone and thalidomide (MPT) and MP by pooling results on RR, PFS and OS reported in all the identified randomized controlled trials (RCTs) under a random effects model. Overall, six prospective RCTs, with data extractable from five published trials (n1568) were identified. The pooled odds ratio of responding to therapy with MPT vs MP was 3.39 (P0.001, 95% CI: 2.24-5.12). The pooled hazard ratios for PFS and OS were and 0.68 (P0.001; 95% CI: 0.55-0.82) and 0.80 (P0.07; 95% CI: 0.63-1.02), respectively, in favor of MPT. The odds ratios for high grade peripheral neuropathy and deep venous thrombosis were 6.6 and 2.4, respectively, in favour of MP. There was significant heterogeneity among the RCTs. Our meta-analysis demonstrates that in previously untreated, transplant ineligible, elderly myeloma patients, the addition of T to MP results in significantly improved RR and PFS with a trend towards improvement in OS compared with MP alone, but at a cost of significantly greater toxicity.

Original language	English (US)
Pages (from-to)	689-696
Number of pages	8
Journal	Leukemia
Volume	25
Issue number	4
DOIs	https://doi.org/10.1038/leu.2010.313
State	Published - Apr 2011

Keywords

elderly
meta-analysis
multiple myeloma
therapy

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1038/leu.2010.313

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Kapoor, P., Rajkumar, S. V., Dispenzieri, A., Gertz, M. A., Lacy, M. Q., Dingli, D., Mikhael, J. R., Roy, V., Kyle, R. A., Greipp, P. R., Kumar, S., & Mandrekar, S. J. (2011). Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: A meta-analysis. Leukemia, 25(4), 689-696. https://doi.org/10.1038/leu.2010.313

Kapoor, P , Rajkumar, SV , Dispenzieri, A , Gertz, MA , Lacy, MQ , Dingli, D, Mikhael, JR, Roy, V, Kyle, RA, Greipp, PR, Kumar, S & Mandrekar, SJ 2011, 'Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: A meta-analysis', Leukemia, vol. 25, no. 4, pp. 689-696. https://doi.org/10.1038/leu.2010.313

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title = "Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: A meta-analysis",

abstract = "Trials comparing efficacy of melphalan prednisone (MP) with MP plus thalidomide in transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. Although there is agreement regarding improved response rates (RRs) and higher toxicity with the addition of thalidomide to MP, the impact on progression free survival (PFS) and overall survival (OS) is less clear. We performed a meta-analysis comparing efficacy of melphalan, prednisone and thalidomide (MPT) and MP by pooling results on RR, PFS and OS reported in all the identified randomized controlled trials (RCTs) under a random effects model. Overall, six prospective RCTs, with data extractable from five published trials (n1568) were identified. The pooled odds ratio of responding to therapy with MPT vs MP was 3.39 (P0.001, 95% CI: 2.24-5.12). The pooled hazard ratios for PFS and OS were and 0.68 (P0.001; 95% CI: 0.55-0.82) and 0.80 (P0.07; 95% CI: 0.63-1.02), respectively, in favor of MPT. The odds ratios for high grade peripheral neuropathy and deep venous thrombosis were 6.6 and 2.4, respectively, in favour of MP. There was significant heterogeneity among the RCTs. Our meta-analysis demonstrates that in previously untreated, transplant ineligible, elderly myeloma patients, the addition of T to MP results in significantly improved RR and PFS with a trend towards improvement in OS compared with MP alone, but at a cost of significantly greater toxicity.",

keywords = "elderly, meta-analysis, multiple myeloma, therapy",

author = "P. Kapoor and Rajkumar, {S. V.} and A. Dispenzieri and Gertz, {M. A.} and Lacy, {M. Q.} and D. Dingli and Mikhael, {J. R.} and V. Roy and Kyle, {R. A.} and Greipp, {P. R.} and S. Kumar and Mandrekar, {S. J.}",

note = "Funding Information: This work was supported in part by the National Cancer Institute, National Institutes of Health Grants CA62242 and CA15083. Funding Information: Shaji Kumar receives research support for clinical trials from Celgene, Novartis, Millennium, Bayer, Genzyme, Merck and Cephalon. Angela Dispenzieri and Martha Q Lacy receive research funding from Celgene. Philip R Greipp receives research-funding grants from Celgene and Novartis, and is on the advisory board of Amgen. Morie A Gertz receives research support from Millennium and Novartis, and honorarium from Celgene and Millennium. Robert A Kyle has been on the disease and/or data monitoring committees of Celgene, Novartis, Merck, Bristol-Myers Squibb Keryx Biopharmaceuticals, Onyx Pharma- ceuticals and Johnson and Johnson sponsored studies. He is also a consultant for Millennium and receives honoraria from Binding Site. The remaining authors have no conflicts of interest to declare.",

year = "2011",

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doi = "10.1038/leu.2010.313",

language = "English (US)",

volume = "25",

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T1 - Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma

T2 - A meta-analysis

AU - Kapoor, P.

AU - Rajkumar, S. V.

AU - Dispenzieri, A.

AU - Gertz, M. A.

AU - Lacy, M. Q.

AU - Dingli, D.

AU - Mikhael, J. R.

AU - Roy, V.

AU - Kyle, R. A.

AU - Greipp, P. R.

AU - Kumar, S.

AU - Mandrekar, S. J.

N1 - Funding Information: This work was supported in part by the National Cancer Institute, National Institutes of Health Grants CA62242 and CA15083. Funding Information: Shaji Kumar receives research support for clinical trials from Celgene, Novartis, Millennium, Bayer, Genzyme, Merck and Cephalon. Angela Dispenzieri and Martha Q Lacy receive research funding from Celgene. Philip R Greipp receives research-funding grants from Celgene and Novartis, and is on the advisory board of Amgen. Morie A Gertz receives research support from Millennium and Novartis, and honorarium from Celgene and Millennium. Robert A Kyle has been on the disease and/or data monitoring committees of Celgene, Novartis, Merck, Bristol-Myers Squibb Keryx Biopharmaceuticals, Onyx Pharma- ceuticals and Johnson and Johnson sponsored studies. He is also a consultant for Millennium and receives honoraria from Binding Site. The remaining authors have no conflicts of interest to declare.

PY - 2011/4

Y1 - 2011/4

N2 - Trials comparing efficacy of melphalan prednisone (MP) with MP plus thalidomide in transplant ineligible, elderly patients with multiple myeloma have provided conflicting evidence. Although there is agreement regarding improved response rates (RRs) and higher toxicity with the addition of thalidomide to MP, the impact on progression free survival (PFS) and overall survival (OS) is less clear. We performed a meta-analysis comparing efficacy of melphalan, prednisone and thalidomide (MPT) and MP by pooling results on RR, PFS and OS reported in all the identified randomized controlled trials (RCTs) under a random effects model. Overall, six prospective RCTs, with data extractable from five published trials (n1568) were identified. The pooled odds ratio of responding to therapy with MPT vs MP was 3.39 (P0.001, 95% CI: 2.24-5.12). The pooled hazard ratios for PFS and OS were and 0.68 (P0.001; 95% CI: 0.55-0.82) and 0.80 (P0.07; 95% CI: 0.63-1.02), respectively, in favor of MPT. The odds ratios for high grade peripheral neuropathy and deep venous thrombosis were 6.6 and 2.4, respectively, in favour of MP. There was significant heterogeneity among the RCTs. Our meta-analysis demonstrates that in previously untreated, transplant ineligible, elderly myeloma patients, the addition of T to MP results in significantly improved RR and PFS with a trend towards improvement in OS compared with MP alone, but at a cost of significantly greater toxicity.

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Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: A meta-analysis

Abstract

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ASJC Scopus subject areas

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