Efficacy and Safety of High-Dose Chemotherapy with Treosulfan and Melphalan in Multiple Myeloma

Abstract

(1) Background: Upfront treatment consolidation with high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) has relevantly contributed to achieving durable remissions following induction treatment in multiple myeloma (MM) patients. The optimization of HDCT regimens can, therefore, essentially contribute to improving the depth and duration of tumor remissions. To date, melphalan at 200 mg/m2 is the standard HDCT regimen for fit MM patients. In our previous work, we showed promising efficacy and safety results for treosulfan (14 g/m2) and melphalan (200 mg/m2) (TreoMel) in acute myeloid leukemia (AML) patients receiving ASCT. Based on these data, TreoMel became the standard of care for fit MM patients at our institution. (2) Methods: We identified 115 consecutive MM patients who underwent consolidation with TreoMel between 01/2020 and 08/2022 at the University Hospital of Bern. We analyzed the safety and efficacy data, as well as the treosulfan pharmacokinetics, correlating them with tumor responses. (3) Results: A complete response (CR) rate of 84% was achieved, which is comparable to the CR rate reported for the quadruplet combination. The median PFS was 30 months (95% CI: 20.4—not reached), and the 31-month OS rate was 83%. The median area under the curve (AUC) for treosulfan was 952.5 mg*h/L (range: 527.4–1781.4), and the median peak level was 332.3 mg/L (range: 168–554). The treosulfan pharmacokinetics showed no significant correlation with MM responses after HDCT and ASCT. However, female patients had a significantly higher AUC (p = 0.007) and peak value (p = 0.001), and the higher values were associated with longer hospitalizations. (4) Conclusions: Treatment consolidation with TreoMel HDCT demonstrated a promising efficacy and safety profile in our cohort of MM patients and deserves further investigation in prospective studies.

Safety and Efficacy of High-Dose Chemotherapy with TreoMel 200 vs. TreoMel 140 in Acute Myeloid Leukemia Patients Undergoing Autologous Stem Cell Transplantation

“…However, despite more effective and less toxic induction and consolidation regimens, relapse rates and mortality in AML patients remain high, so further optimization of AML first-line treatment is needed. In another study from our group, by Gillich et al [25], we showed that conditioning with Tre-oMel 200 is highly effective and feasible in fit multiple myeloma patients. From September 2021, we modified our institutional HDCT standard for AML patients from TreoMel 140 to TreoMel 200 by increasing the melphalan dose from 140 mg/m 2 to 200 mg/m 2 [15].…”

“…Electrospray ionization was used to introduce the eluent into the mass spectrometer (Xevo TQ-S, Waters Corp., Milford, MA, USA), which operated in positive-ion electrospray ionization (ESI +) mode. Data analysis was performed using TargetLynx (MassLynx software, version 4.1, Waters Corp., Milford, MA, USA), by comparing the area under the specific chromatograms of the MRM and the area of the isotope-labeled analog [15,25,27].…”

“…While the TreoMel regimen has been commonly used with melphalan dosed at 140 mg/m 2 , given the adverse prognosis of AML, we decided to escalate the dosing to 200 mg/m 2 for the patients treated from September 2021. Moreover, since relevant variability in treosulfan pharmacokinetics has been shown in previous studies, with potential impact on HSCT outcome and toxicity, we assessed treosulfan pharmacokinetics in both treatment cohorts [15,16,25,26].…”

Daratumumab during Myeloma Induction Therapy Is Associated with Impaired Stem Cell Mobilization and Prolonged Post-Transplant Hematologic Recovery

“…HDCT procedures were comparable. Most patients received TreoMel based on data gathered in own previous work [51]. The median amount of transplanted CD34+ cells was 9% lower for the D-RVd patients (p = 0.0157), which we interpreted in the context of the lower amount of collected CD34+ cells.…”