Variation in melphalan dosing in myeloma patients undergoing high-dose chemotherapy and autotransplantation

Abstract

7047 Background: Chemotherapy doses are often reduced in obese patients to ameliorate toxicity; a practice shown to result in adverse outcome in breast cancer. The dose of melphalan used before autografting in myeloma correlates with outcome. Because melphalan is widely distributed in the body, exposure of myeloma cells to the drug is likely dependent upon the actual body weight (ABW). We evaluated variability in melphalan dose received by patients in terms of mg/kg ABW and ideal body weight (IBW). Methods: Data on 243 autotransplants for myeloma after 200 mg/m2 melphalan were analyzed retrospectively. The weight value used to calculate body surface area (BSA) using the Dubois formula was the ABW if it was lower than or up to 20% higher than IBW (non-obese). If ABW was >20% above IBW (obese), the value used for BSA calculation was IBW + 25–50% of the difference between ABW and IBW. Results: 191 patients were obese (ABW 20.2% to 104.7% higher than IBW; median 42.8% higher) and 92 were non-obese (ABW 18.3% lower than to 19.5% higher than IBW; median 9.0% higher). The melphalan dose administered was 2.9–6.2 mg/kg ABW (median 4.5) and 4.6–7.5 mg/kg IBW (median 5.6). There was no correlation between the mg/kg IBW and mg/kg ABW doses (r=0.10; P=0.12). The median dose for the obese group was significantly lower than the non-obese group when calculated by ABW (4.0 vs 5.0 mg/kg; range 2.9–5.5 vs 4.4–6.2; P<0.0001). The median dose was higher for the obese group when calculated by IBW (5.8 vs 5.5 mg/kg; range 5.0–7.5 vs 4.6–6.3; P<0.0001). There was a strong inverse correlation (r=0.90; P<0.0001) between the per cent ABW-IBW difference and the melphalan dose in mg/kg ABW - consistent with decreasing drug exposure as the degree of obesity increased. Expectedly, there was a modest direct correlation (r=0.49; P<0.0001) between the per cent ABW-IBW difference and the melphalan dose in mg/kg IBW. Conclusions: The dose of melphalan measured in mg/kg ABW is significantly lower in obese patients than in non-obese patients due to dose-adjustment. Further work is required to see if this affects outcome. No significant financial relationships to disclose.