Outcomes for Patients with Multiple Myeloma after Receipt of Melphalan 200mg/m2 Versus 140 Mg/m2 for Autologous Stem Cell Transplantation

Introduction High-dose melphalan before autologous stem cell transplantation (ASCT) is associated with dose-related adverse effects whereby dose reductions have been suggested for patients of older age and/or impaired renal function; however, no standard criteria for dose reduction exists due to limited data and conflicting evidence. Objectives To evaluate if differences exist between efficacy and safety outcomes after standard dose melphalan (200 mg/m2, Mel200) versus reduced dose of melphalan (140 mg/m2, Mel140) in patients with MM undergoing ASCT, including when stratified by age and renal function. Methods A single-center, IRB-approved, retrospective review of adult patients with MM who underwent their first ASCT between Jan 2010 - Nov 2022 and received Mel200 or Mel140. The primary endpoint was progression-free survival (PFS). Additional secondary efficacy and safety endpoints included relapse rate, overall survival (OS), hospital length of stay, incidence of febrile neutropenia and acute kidney injury, and time to engraftment. Subgroup analyses were performed based on patient age < 65 years versus ≥ 65 years and CrCl 30 – 59 mL/min versus CrCl ≥ 60 mL/min. Statistical analysis via SAS 9.4 employed Chi squared/Fisher's exact, t-test, and Cox proportional hazard models to examine the effect of demographic factors when controlling for other variables. Results A total of 322 patients were included, 240 in the Mel200 group and 82 in the Mel140 group. Baseline demographics were similar between groups except patients receiving Mel140 were on average older, had worse kidney function, and higher MM risk stratification stage versus patients receiving Mel200 (Table 1). 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 compared to those ≥ 65 years of age or for patients with CrCl 30 – 59 mL/min compared to those with CrCl ≥ 60 mL/min in the overall cohort or in either the Mel200 group or the Mel140 groups (all P > 0.05). In the overall cohort, no difference existed in PFS in patients < 65 years versus ≥ 65 years when stratified by CrCl (P > 0.05). No differences existed between Mel200 and Mel140 across all secondary outcomes (Table 2; all P > 0.05). In the Cox proportional hazard model, disease status pre-transplant and high cytogenetic risk had significant effects on PFS when controlling for dose, performance status, MM risk stratification score (P = 0.0186 and P = 0.0175 respectively). Conclusions Reduced dose melphalan (140 mg/m2) prior to ASCT for patients with MM showed no differences in safety or efficacy outcomes compared to standard doses of melphalan (200 mg/m2) even when analyzed based on age and renal function. Larger randomized controlled trials are needed to validate these findings. Careful patient selection for dose reduction should be considered.