日本人多発性骨髄腫患者における大量メルファラン療法の有害事象と薬物曝露量の関係

抄録

High-dose melphalan is one of the most active agents for the treatment of multiple myeloma but is associated with numerous toxicities, including myelosuppression, mucositis, diarrhea, nausea, and vomiting. This study aimed to retrospectively examine the relationship between melphalan exposure and adverse events in 19 Japanese patients with multiple myeloma receiving high-dose melphalan. The area under the curve (AUC) using the population pharmacokinetic model derived parameters was estimated. The mean (SD) estimated total and unbound melphalan AUC were 10.7 (1.6) mg･h/L and 2.3 (0.3) mg･h/L, respectively. The total AUC and unbound AUC were significantly higher in patients with severe diarrhea (≥ grade 3). Thus, high-dose melphalan exposure is associated with the risk of toxicity in Japanese patients with multiple myeloma. The estimated AUC may be able to predict serious toxicities among patients treated with high dose melphalan.