Assessing Outcomes in Patients with Multiple Myeloma Post-Autologous Stem Cell Transplantation: Contrasting the Effects of Melphalan Dosages at 200mg/m2 versus 140mg/m2

Background No standard criteria for dose reduction exists for high-dose melphalan for autologous stem cell transplantation (ASCT) for multiple myeloma (MM) due to limited and conflicting evidence. Objective To evaluate efficacy and safety of standard dose (200 mg/m2=Mel200) versus reduced dose (140 mg/m2=Mel140) of melphalan in patients with MM undergoing ASCT. Design : A single-center retrospective review of adults with MM for their first ASCT between January 1, 2010, and November 1, 2022, who received Mel200 or Mel140 as conditioning. Primary endpoint was progression-free survival (PFS). Secondary safety and efficacy endpoints included overall survival (OS), incidence of febrile neutropenia and acute kidney injury, and time to engraftment. Subgroup analyses were performed based on patient age and renal function. Results A total of 322 patients were included in the study, 240 in the Mel200 group and 82 in the Mel140 group. Baseline demographics were similar except patients receiving Mel140 were on average older and had worse kidney function. PFS at 2 years was not different between groups (P = 0.2335). No difference existed in 2-year PFS or OS for patients <65 years of age versus ≥65 years of age or for patients with CrCl 30–59 mL/min versus CrCl ≥60 mL/min within either Mel200 group or Mel140 group (all P > 0.05). No differences existed between groups across all secondary outcomes. Conclusion Reduced doses melphalan showed no differences in safety or efficacy outcomes versus standard dose even when analyzed based on age and renal function. Larger randomized controlled trials need to be performed to validate these findings. Micro-Abstract Despite varied evidence and lack of specific thresholds, dose reduction of melphalan before autologous transplantation is considered for patients of older age or reduced renal function. This retrospective study of 322 patients compared melphalan 200mg/m2 vs 140mg/m2 finding no differences in efficacy, such as 2-year progression-free survival, or safety outcomes between groups, including when analyzed by age and renal function.