Factors Associated with Dose Modification of Lenalidomide Plus Dexamethasone Therapy in Multiple Myeloma

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  • Kado Yoko
    Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University Department of Pharmacy, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Tsujimoto Masayuki
    Department of Clinical Pharmacy, Kyoto Pharmaceutical University
  • Fuchida Shin-ichi
    Department of Hematology, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Okano Akira
    Department of Hematology, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Hatsuse Mayumi
    Department of Hematology, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Murakami Satoshi
    Department of Hematology, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Sugii Hikofumi
    Department of Pharmacy, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Ueda Kumi
    Department of Pharmacy, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Toda Yuki
    Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University
  • Minegaki Tetsuya
    Department of Clinical Pharmacy, Kyoto Pharmaceutical University
  • Nishiguchi Kohshi
    Department of Clinical Pharmacy, Kyoto Pharmaceutical University
  • Muraki Yuichi
    Department of Clinical Pharmacoepidemiological, Kyoto Pharmaceutical University
  • Shimazaki Chihiro
    Department of Hematology, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center
  • Ashihara Eishi
    Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University

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Abstract

<p>Long-term combination treatment with lenalidomide and low-dose dexamethasone is important to achieve a curative effect in patients with multiple myeloma (MM). In this study, the plasma concentration of lenalidomide was measured at 3 h after oral administration, when the drug is in the elimination phase and can be easily measured in outpatients, to identify factors that may lead to the discontinuation of this combination therapy. Patients were assigned to continuation or discontinuation of therapy groups, and the baseline characteristics of patients, lenalidomide concentration, and concentration/dose (C/D) ratios reflecting oral clearance were compared between the two groups. The efficacy and severity of adverse events were also compared. The results showed that patients who discontinued or modified treatment had low plasma concentrations of lenalidomide and C/D ratios, indicating high oral clearance of lenalidomide. The estimated creatinine clearance rate was negatively correlated with the C/D ratio. The plasma concentrations of lenalidomide were independent from kidney function and differed significantly among patients. Taken together, the results indicate that low plasma concentrations of lenalidomide and low C/D ratios may lead to discontinuation of combination therapy in patients with MM. This suggests that early measurement of lenalidomide plasma continuation would help to prevent discontinuation of therapy or a delay in modifying the dose of lenalidomide.</p>

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