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Plasma Cell Disorders

A randomized study of melphalan 200 mg/m2 vs 280 mg/m2 as a preparative regimen for patients with multiple myeloma undergoing auto-SCT

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Abstract

We aimed to examine whether doses of melphalan higher than 200 mg/m2 improve response rates when used as conditioning before autologous transplant (ASCT) in multiple myeloma (MM) patients. Patients with MM, n=131, were randomized to 200 mg/m2 (mel200) vs 280 mg/m2 (mel280) using amifostine pretreatment. The primary end point was the proportion of patients achieving near complete response (⩾nCR). No treatment-related deaths occurred in this study. Responses following ASCT were for mel200 vs mel280, respectively, ⩾nCR 22 vs 39%, P=0.03, ⩾PR 57 vs 74%, P=0.04. The hazard of mortality was not statistically significantly different between groups (mel200 vs mel280; hazard ratio (HR)=1.15 (95% confidence interval (CI), 0.62–2.13, P=0.66)) nor was the rate of progression/mortality (HR=0.81 (0.52–1.27, P=0.36)). The estimated PFS at 1 and 3 years were 83 and 46%, respectively, for mel200 and 78 and 54%, respectively, for mel280. Amifostine and mel280 were well tolerated, with no grade 4 regimen-related toxicities and only one grade 3 mucositis (none with mel200) and three grade 3 gastrointestinal (GI) toxicities (two in mel200). Hospitalization rates were more frequent in the mel280 group (59 vs 43%, P=0.08). Mel280 resulted in a higher major response rate (CR+nCR) and should be evaluated in larger studies.

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Acknowledgements

This study was supported in part by research funds supplied by Astra-Zeneca, R21 CA155911-01, and by P01 CA18029-28 both from NIH/NCI. Previously published at the 2012 ASH Annual Meeting, Atlanta, GA December 2012. This study was supported in part by resources of the VA Puget Sound Health Care System, Seattle, WA.

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Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center,, Seattle,, WA, USA

    W I Bensinger, T A Gooley, D G Maloney, A K Gopal, D J Green, O W Press & L A Holmberg

  2. University of Washington,, Seattle,, WA, USA

    W I Bensinger, P S Becker, T A Gooley, T R Chauncey, D G Maloney, A K Gopal, D J Green, O W Press & L A Holmberg

  3. VA Puget Sound Health Care System,, Seattle,, WA, USA

    T R Chauncey

  4. Cedars Sinai Medical Center,, Los Angeles,, CA, USA

    M Lill & R Vescio

  5. James P Wilmot Cancer Center, University of Rochester,, Rochester, NY, USA

    J J Ifthikharuddin

  6. Wake Forest Baptist Medical Center, Winston-Salem, NC, USA

    G L Phillips

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  1. W I Bensinger
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  2. P S Becker
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  3. T A Gooley
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  10. J J Ifthikharuddin
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  12. L A Holmberg
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  13. G L Phillips
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Correspondence to W I Bensinger.

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Competing interests

WB received research funding for this trial from Astra-Zeneca.

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Bensinger, W., Becker, P., Gooley, T. et al. A randomized study of melphalan 200 mg/m2 vs 280 mg/m2 as a preparative regimen for patients with multiple myeloma undergoing auto-SCT. Bone Marrow Transplant 51, 67–71 (2016). https://doi.org/10.1038/bmt.2015.211

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