Comparison of Outcomes Post Autologous Stem Cell Transplant (ASCT) in Patients with Multiple Myeloma (MM) Based on Dosage of Melphalan (mel) As Part of Conditioning Therapy: Single Institutional Experience of a Large Study Group

Abstract

<h3>Introduction</h3> High dose chemotherapy followed by ASCT is the standard of care in the treatment of eligible patients with MM. Melphalan has been the drug of choice for conditioning therapy at a dose of 200 mg/m² (mel 200). However, for elderly patients (older than 65 years) and renal dysfunction (serum creatinine>2), a reduced dose of 140 mg/m² (mel 140) is commonly used based on a prior retrospective study. We conducted a retrospective analysis comparing the outcomes of patients with MM who underwent ASCT at our institution at the standard dose of melphalan versus reduced dose. <h3>Objectives</h3> 1) Compare efficacy of melphalan 200mg/m² versus 140mg/m² for ASCT in MM. 2) Assess impact of age and renal dysfunction on the outcome in MM. 3) Compare the clinical characteristics of patients who underwent ASCT. <h3>Methods</h3> We performed a retrospective analysis of 1002 consecutive patients with newly diagnosed MM who underwent ASCT at The Ohio State University between 1992 through 2016. Data were collected regarding patient demographics, disease characteristics, therapy received, dose of melphalan conditioning and clinical outcomes. Progression-free survival (PFS) was defined from time of transplantation to disease progression or death, censoring those alive without progression at the last contact. Overall survival (OS) was calculated from the time of transplantation to death, censoring those alive at last contact. PFS and OS were estimated using Kaplan-Meier method. Log-rank tests were used to compare PFS and OS between the groups, and Cox proportional hazard models were used to estimate the hazard ratios (HR). <h3>Results</h3> 946 patients received high dose melphalan conditioning prior to ASCT, of which 807 patients received mel 200 while 126 patients received mel 140. Thirteen patients were excluded due to alternate dosing. Around 16% of patients in the mel 200 group were older than 65 years compared to 42.1% in the mel 140 group. More patients in the mel 140 group had ISS stage 3 MM compared to mel 200 (64.7% vs 24.6%). Renal dysfunction was seen in 69.8% of patients in the mel 140 group while 15.5% had it in the mel 200 group. PFS of patients who received mel 140 was not inferior to those who received mel 200 (p=0.29, figure 1). Overall survival of patients who received mel 200 was better than those who got mel 140 by univariate analysis (p=0.048, figure 1). However, after adjusting for age, ISS staging and renal dysfunction, the difference in OS was not significant. <h3>Conclusion</h3> Patients who got mel 140 did no worse than those who received mel 200 in terms of disease outcome as assessed by PFS and OS.