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Myeloma

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

Leukemia volume 25, pages 689–696 (2011)Cite this article

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A Corrigendum to this article was published on 07 September 2011

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 (n=1568) were identified. The pooled odds ratio of responding to therapy with MPT vs MP was 3.39 (P<0.001, 95% CI: 2.24–5.12). The pooled hazard ratios for PFS and OS were and 0.68 (P<0.001; 95% CI: 0.55–0.82) and 0.80 (P=0.07; 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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Acknowledgements

This work was supported in part by the National Cancer Institute, National Institutes of Health Grants CA62242 and CA15083.

Author Contributions

SVR and SK conceived the study; PK, SVR, SK and SJM collected the data; PK, SJM and SK wrote the manuscript; SJM performed statistical analysis; SJM, PK, SK, MQL, AD, MAG, JRM, DD, VR, RAK, PRG and SVR interpreted the data; SVR, DD, AD, MQ L, JRM, MAG, PRG and RAK edited the manuscript.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    P Kapoor, S V Rajkumar, A Dispenzieri, M A Gertz, M Q Lacy, D Dingli, R A Kyle, P R Greipp & S Kumar

  2. Division of Hematology/Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA

    J R Mikhael

  3. Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, USA

    V Roy

  4. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

    S J Mandrekar

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Correspondence to S J Mandrekar.

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Competing interests

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 Pharmaceuticals 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.

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Kapoor, P., Rajkumar, S., Dispenzieri, A. et al. Melphalan and prednisone versus melphalan, prednisone and thalidomide for elderly and/or transplant ineligible patients with multiple myeloma: a meta-analysis. Leukemia 25, 689–696 (2011). https://doi.org/10.1038/leu.2010.313

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