P-139: Impact of Melphalan Staggered Dosing Prior to Autologous Hematopoietic Cell Transplantation for Multiple Myeloma Patients

Introduction: Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of plasma cells in the bone marrow. The standard of care treatment for eligible patients with newly diagnosed, symptomatic MM after induction therapy is conditioning with high-dose melphalan followed by autologous hematopoietic cell transplantation (auto-HCT). Currently, the standard melphalan dosing regimen is 100 mg/m2 given on Day -2 and Day -1. However, due to melphalan’s stability issues, preparation of this dosing strategy can cause increase cost and drug waste. To reduce high cost and waste associated with chemotherapeutic agents, Hematology/Oncology Pharmacy Association (HOPA) recommends cytotoxic agents be considered for dose rounding if within 5% to 10% of the prescribed dose.

Due to melphalan’s short stability and high cost, our hospital investigated dose rounding using a staggered melphalan dosing approach. The total ordered dose (200 mg/m2) was rounded to the nearest vial size if the difference between the total dose and nearest vial size is less than or equal to 5%. Day -2 and Day -1 doses were determined by splitting the rounded total dose so that each day used an entire vial.

Methods: This study is a single-center, retrospective chart review assessing the efficacy and safety of staggered melphalan dosing compared to standard melphalan dosing. Admitted patients receiving high-dose melphalan prior to auto-HCT from January 1st, 2021, through June 30th, 2022, were included. Patients with systemic light chain amyloidosis and patients receiving tandem auto-HCT were excluded. Data was obtained from patient electronic medical records and CIMBTR records. A cox regression was used to evaluate the time to neutrophil and platelet engraftment. Descriptive statistics were used to evaluate all other outcomes. This study is IRB exempted.

Results: A total of 148 patients were included; 102 patients received staggered melphalan dosing and 46 patients received standard melphalan dosing. Doses were rounded between 0.5 to 5.7% and most doses were rounded down. Baseline characteristics were similar across both groups. There was not a significant difference in the median time to neutrophil engraftment (HR 0.98; p-value 0.93) nor platelet engraftment (HR 1.13; p-value 0.5). There was not a significant difference between the rate of mucositis, diarrhea, nausea, and vomiting. A significantly higher number of patients in the standard melphalan group developed sepsis (3 vs. 0; p-value 0.03). Rates of disease progression and mortality were similar between the two groups. Implementation of staggered melphalan dosing allowed our hospital to save 119 vials and ~$180,000 within the 1.5 years of this study.

Conclusions: Staggered melphalan dosing is an effective and safe method and results in cost savings and waste reduction for transplant institutions.