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

A meta-analysis

Research output: Contribution to journalArticle

83 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)689-696
Number of pages8
JournalLeukemia
Volume25
Issue number4
DOIs
StatePublished - Apr 2011

Fingerprint

Melphalan
Thalidomide
Prednisone
Multiple Myeloma
Meta-Analysis
Transplants
Disease-Free Survival
Survival
Randomized Controlled Trials
Odds Ratio
Peripheral Nervous System Diseases
Venous Thrombosis

Keywords

  • elderly
  • meta-analysis
  • multiple myeloma
  • therapy

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

@article{faaf94a4a1454af9b641e43c594ba374,
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 = "Prashant Kapoor and Rajkumar, {S Vincent} and Angela Dispenzieri and Morie Gertz and Martha Lacy and Dingli, {David M} and Mikhael, {Joseph R} and Vivek Roy and Kyle, {R. A.} and Greipp, {P. R.} and Kumar, {Shaji K} and Mandrekar, {Sumithra J}",
year = "2011",
month = "4",
doi = "10.1038/leu.2010.313",
language = "English (US)",
volume = "25",
pages = "689--696",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

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, Prashant

AU - Rajkumar, S Vincent

AU - Dispenzieri, Angela

AU - Gertz, Morie

AU - Lacy, Martha

AU - Dingli, David M

AU - Mikhael, Joseph R

AU - Roy, Vivek

AU - Kyle, R. A.

AU - Greipp, P. R.

AU - Kumar, Shaji K

AU - Mandrekar, Sumithra J

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.

AB - 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.

KW - elderly

KW - meta-analysis

KW - multiple myeloma

KW - therapy

UR - http://www.scopus.com/inward/record.url?scp=79954448518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954448518&partnerID=8YFLogxK

U2 - 10.1038/leu.2010.313

DO - 10.1038/leu.2010.313

M3 - Article

VL - 25

SP - 689

EP - 696

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 4

ER -