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• W1997392914 abstract "High dose melphalan is the most common regimen for autologous stem cell transplantation (ASCT) for multiple myeloma (MM), but toxicity and efficacy are variable. We hypothesized that variation in body size, body composition, and renal function would explain differences in melphalan pharmacokinetics and therefore in outcomes after transplant. We evaluated 41 patients who received melphalan 200 mg/m2 on day -2 (one patient with poor renal function received 180 mg/m2). We calculated melphalan doses using ideal body weight (IBW), using adjusted IBW (ABW) for patients weighing >120% of IBW. We measured body composition using dual x-ray absorptiometry (DEXA), renal function with both iohexol clearance (Cliohexol) and the Cockroft-Gault formula (CrClCG), and plasma melphalan concentrations using HPLC/tandem mass spectrometry. We used non-compartmental analysis to estimate melphalan clearance (ClMEL) and area under the curve (AUCMEL) and linear regression modeling to identify factors associated with melphalan pharmacokinetics. Patients' mean BSA using actual weight was 1.93 m2 (range 1.44-2.48). By DEXA scan, the mean lean body weight was 53.3 kg (SD 11.0) and mean fat percentage 31% (SD 9.5%). Mean iohexol clearance was 109 mL/min (range 28-163). AUCMEL varied significantly, with a range of 7.6-26.6 mg*h/L (mean 13.6, SD 3.8); ClMEL was similarly variable (mean 27.9 mL/min, SD 8.1). In univariate analyses, ClMEL was inversely related to age and directly related to weight, BSA, lean body weight, bone mineral content, Cliohexol, CrClCG, and MEL dose. ClMEL was not associated with body fat percentage, body fat weight, or body lean percentage, or with other measurements, such as hemoglobin, albumin, immunoglobulins, or M-spike. The strongest correlation with ClMEL was for CrClCG, and multivariable models showed no improved prediction of ClMEL with the addition of other factors to CrClCG. The best model for predicting AUCMEL was dose/CrClCG (see table). These models consistently under-predicted AUCMEL (mean prediction error -3.3% to -2.6%).TablePerformance of linear models predicting AUCMELModelR2p-valuedose/CrClCG0.260.001dose/Cliohexol0.110.04dose/weight0.100.04dose/lean weight0.080.08dose/BSAIBW0.060.11dose/BSAABW0.040.23 Open table in a new tab A composite calculation incorporating age, weight, and serum creatinine, like CrClCG, may be the best way to choose melphalan doses but only explains 26% of drug exposure variability. Other measures of body composition were poor predictors of exposure. Further research is needed to better address the remaining variability in drug clearance and exposure." @default.
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• W1997392914 date "2012-02-01" @default.
• W1997392914 modified "2023-10-01" @default.
• W1997392914 title "Effect of Body Composition and Renal Function on the Pharmacokinetics of High-Dose Melphalan for Multiple Myeloma" @default.
• W1997392914 doi "https://doi.org/10.1016/j.bbmt.2011.12.131" @default.
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