Relationship between Adverse Events and AUC in Japanese Patients with Multiple Myeloma Receiving High-dose Melphalan

Abstract

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.