Reduced-dose melphalan vs. standard dose melphalan for autologous stem cell transplantation: Is there a difference in outcome?

Background: Based on the results of randomized phase III trials, melphalan 200 mg/m2 IV (MEL 200) is considered the standard preparative regimen for autologous hematopoietic stem cell transplantation (auto-HCT) for multiple myeloma. However, reduced doses of melphalan, 140 mg/m2 (MEL 140) or 180 mg/m2 (MEL 180), are often used in older patients or patients with renal dysfunction. Methods: The primary objective was to determine if there was a difference in toxicity, treatment-related mortality, response rate, progression- free survival or overall survival in patients that received lower doses of melphalan for auto-HCT. From June 1, 1996 through December 25, 2010, 1425 patients received auto-HCT at our institution. We identified 57 patients that received MEL 140 or 180 and compared their outcomes with a control group (approximately 4:1) of patients who received MEL 200. Patients were matched for the year of transplant, chemosensitivity, disease status at auto-HCT and time from diagnosis to auto-HCT. Results: Preparative regimens were MEL 140 (19 patients), MEL180 (38 patients) and MEL 200 (253 patients). Patients in MEL140 group were older (median age 70), with 58% patients older than 65 at auto-HCT (p = 0.0001). Median serum creatinine level (1.71 mg/dl) was higher in the MEL 140 group (p = 0.007). There was no significant difference in disease status (p = 0.38) or chemosensitivity (p = 0.28) between the 3 groups. Median times to neutrophil engraftment in MEL 140, 180 and 200 were 11, 10 and 10 days, respectively (p =0.15). Transplant-related mortality at 100 days was 0%, 2% and 0.8% in MEL 140, 180 and 200, respectively (p = 1.0). Complete remission (CR) + very good partial remission (VGPR) were seen in 42%, 37% and 45% in Mel 140, 180 and 200, respectively (p = 0.45). The overall response rate (CR + VGPR + PR) was 89%, 71% and 82% in MEL 140, 180 and 200, respectively (p = 0.54). Median follow up in surviving patients in Mel 140, 180 and 200 was 13.8, 24.3 and 18.3 months, respectively. There was no significant difference in time to progression (p = 0.27) between Mel 140, 180 or 200. Kaplan-Meier estimates of 2-year progression- free survival were 69%, 72% and 52% (p = 0.74), and 2-year overall survival were 69%, 83% and 83% (p = 0.48) in Mel 140, 180 and 200, respectively. Conclusion: The dose of melphalan can be safely reduced to 140 mg/m2 in older patients or patients with renal insufficiency without adversely impacting the response rate, duration of remission or survival.