Pharmacokinetics and outcome of high-dose melphalan followed by autologous stem cell transplantation in dialysis-dependent patients with multiple myeloma

Abstract

High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for fit patients with multiple myeloma (MM). However, individuals who are dependent on hemodialysis are frequently excluded from ASCT. Recommendations on chemotherapy dosing and hemodialysis scheduling vary in literature and definite conclusions are impeded by the heterogeneity of cohorts. We aimed to evaluate the safety and efficacy of ASCT in patients with MM and end-stage renal disease and to examine the pharmacokinetics of melphalan on a fixed schedule of melphalan infusion and hemodialysis. The outcome of 13 patients undergoing ASCT while being on hemodialysis between 2000 and 2022 was retrospectively analysed and compared to matched hemodialysis-independent patients. Melphalan plasma concentrations were measured in 4 hemodialysis-dependent and 5 independent patients. Plasma concentrations of hemodialysis-dependent patients were comparable to hemodialysis-independent patients with a 6-hour interval between melphalan infusion and hemodialysis (p = 0.9). The rate of immediate side effects of high-dose melphalan was significantly higher in 13 dialysis-dependent patients compared to 47 matched controls despite not having prolonged neutropenia (p = 0.9). Overall survival both from d₀ of ASCT and diagnosis was comparable (p = 0.33 and p = 0.17, respectively). Thus, adopting the proposed schedule and management of immediate side effects make ASCT a safe option for myeloma patients with end-stage renal disease.

Keywords: Autologous stem cell transplantation; Hemodialysis; High-dose melphalan; Multiple myeloma.

Fig. 1

Overall survival of hemodialysis-dependent patients in comparison to matched hemodialysis-independent patients. (A) OS calculated from diagnosis and (B) calculated from d₀ of ASCT. Abbreviations: HD, hemodialysis.

Fig. 2

Melphalan plasma concentrations of hemodialysis-patients compared with dialysis-independent patients. (A) Line graph representing the mean melphalan concentration and standard deviation at each given time point for hemodialysis-dependent patients. t1 = before melphalan day 1, t2 = after melphalan day1, t3 = before dialysis day 2, t4 = after dialysis day 2, t5 = before melphalan day 2, t6 = after melphalan day 2, t7 = before dialysis day 2, t8 = after dialysis day 2, t9 = trough level 20 h after melphalan. (B) Line graph representing the mean melphalan concentration and standard deviation at each given time point for non-hemodialysis patients, t1 = before melphalan day 1, t2 = after melphalan day1, t5 = before melphalan day 2, t6 = after melphalan day 2, t9 = trough level 20 h after melphalan, (C) Boxplot comparing the AUC of hemodialysis- and non-hemodialysis patients Abbreviations: HD, hemodialysis; AUC, area under curve.