Effect of Melphalan 140 Mg/m² Versus 200 Mg/m² on Toxicities and Outcomes in Multiple Myeloma Patients Undergoing Single Autologous Stem Cell Transplantation

Introduction: Although melphalan at a dose of 140 mg/m² (MEL-140) is known to be an effective preparative regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients, there are very few studies comparing it to the most commonly used dose of 200 mg/m² ( MEL-200).

Methods: We retrospectively reviewed the records of all myeloma patients who underwent an ASCT between 2001 and 2010 at our institution. We then identified patients who received melphalan as their preparative regimen at doses of 140 mg/m² or 200 mg/m². Patients who received any other drug as conditioning regimen or had more than one ASCT or had documented amyloidosis were excluded. Data were collected for variables known to possibly affect prognosis of MM patients. We assessed effect of melphalan dose on toxicities and outcomes.

Results: A total of 129 eligible patients were identified, with 33 receiving MEL-140 and 96 receiving MEL-200. As was expected significantly higher percentage of patients in the MEL-140 arm were older than 65 years (P=<0.001) or had cardiac ejection fraction < 50 (P=0.0001) or had Karnofsky score < 80 (P=0.01) or had creatinine > 2 either at diagnosis (P=0.004) or the time of ASCT (P=0.001). Rest of the patient and disease characteristics including Durie-Salmon stage, myeloma subtype and disease status at ASCT were not significantly different between the 2 arms. Patients in MEL-140 needed significantly longer time to ANC engraftment (P=0.037) and also had significantly higher frequency of neutropenic fever (P=0.003). There were no significant differences in mucositis (including grade), nausea, vomiting, diarrhea, bacteremia, or length of hospital stay and frequency of repeat hospitalizations among both groups. There was no treatment related mortality in either group. At a median follow up of 74 months (range, 52-140) from ASCT, there were no significant differences in relapse free survival (RFS) (P=0.4988) and overall survival (OS) (P=0.6936) between the two groups. Five year OS for MEL-140 and MEL-200 is 71.6% and 78.9%, while RFS is 23.9% and 34%, respectively. Proportion of patients whose myeloma status improved to ≥ VGPR at 3 months post ASCT was also not different (P=0.385). Importantly, similar proportions of patients received various post ASCT maintenance therapy (P=0.605). In multivariate cox proportional hazards model only disease status of ≥VGPR at the time of ASCT significantly affected RFS (P=0.024) but did not impact OS (P=0.104).

Conclusion: MM patients who received MEL-140 had similar long term outcomes as those who received MEL-200 despite their older age, lower performance status and renal insufficiency.