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Pretransplant hemoglobin and creatinine clearance correlate with treatment-free survival after autologous stem cell transplantation for multiple myeloma

Bone Marrow Transplantation volume 54, pages 2081–2087 (2019)Cite this article

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Abstract

Melphalan is given at a dose of 200 mg/m2 (Mel200) prior to ASCT for multiple myeloma (MM). Pharmacokinetic (PK) studies show a high degree of interpatient variability. We aimed to test the impact of clinical factors previously shown to affect melphalan PK such as hemoglobin (Hgb), fat-free mass (FFM), and creatinine clearance (CrCl) on outcomes. Median Hgb (from day −2 to −1) and FFM were grouped as low or high relative to their sample medians, and CrCl was divided into ≥60 or <60 ml/min. In 133 MM patients, median TFS (defined as time from ASCT to initiation of next subsequent line of therapy or death) was longer in patients with lower Hgb (35 vs. 16 months, p = 0.02). Patients with both lower Hgb and CrCl experienced longer TFS compared to those with higher Hgb and CrCl (35 vs. 13 months, p = 0.03). In multivariate analysis, lower hemoglobin, lower CrCl, and a combined low hemoglobin and CrCl were strongly associated with improved TFS. Patients with a lower hemoglobin or creatinine clearance experienced significantly more toxicity. We show for the first time that Hgb and CrCl are important predictors of outcomes after Mel200. PK-directed melphalan dosing may be beneficial in achieving optimal outcomes.

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Acknowledgements

GSC was supported by the National Institutes of Health, National Heart, Lung and Blood Institute through grant number R21HL140531.

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Authors and Affiliations

  1. Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA

    Karen Sweiss & Jeremy J. Johnson

  2. Cancer Center, University of Illinois, Chicago, IL, USA

    Karen Sweiss, Jeremy J. Johnson, Damiano Rondelli & Pritesh R. Patel

  3. Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL, USA

    Gregory S. Calip

  4. Division of Hematology and Oncology, University of Illinois at Chicago, Chicago, IL, USA

    Damiano Rondelli & Pritesh R. Patel

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  1. Karen Sweiss
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Correspondence to Karen Sweiss.

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PRP receives honoraria from Celgene, Janssen, and Amgen and consulting fees from Celgene and Amgen.

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Sweiss, K., Calip, G.S., Johnson, J.J. et al. Pretransplant hemoglobin and creatinine clearance correlate with treatment-free survival after autologous stem cell transplantation for multiple myeloma. Bone Marrow Transplant 54, 2081–2087 (2019). https://doi.org/10.1038/s41409-019-0628-8

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  • DOI: https://doi.org/10.1038/s41409-019-0628-8

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