A Lower Dose of Melphalan (140 mg/m2) As Preparative Regimen for Multiple Myeloma in Patients >65 or with Renal Dysfunction

Background: Melphalan at a dose of 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 such as140 mg/m² IV (MEL 140) are often used in older patients or patients with renal dysfunction.

Methods: The purpose of this retrospective analysis was to determine if there was a difference in toxicity, treatment-related mortality (TRM), response rate, progression- free survival (PFS) or overall survival (OS) in patients that received 140 mg/m² of melphalan (MEL 140) compared to those receiving MEL 200 for auto-HCT.  From June 1, 1996 through December 31, 2012, 63 patients received MEL 140. We compared their outcomes with 252 patients that received MEL 200.

Results: Patients in the MEL 140 group were older (median age 71 vs. 62; P<0.0001), had a higher median β2 microglobulin (β2M) level both at diagnosis (5.5 vs. 3.7; p=0.0002) and auto-HCT (4 vs. 2.5; p<0.0001), and had a higher median serum creatinine (Cr) at auto-HCT (1.3 vs. 1.05; p=0.05).  A higher proportion of patients in MEL 140 were older than 65 with serum Cr > 2 mg/dL. There was no significant difference in disease status or high-risk cytogenetics between the 2 groups. NCI CTCv3 > grade III non-hematologic toxicity was not significantly different between MEL 140 and MEL 200. TRM at 100 days and at 1 year was 0% and 0.4% in MEL 140 and 200 (p=1.0), respectively. Complete remission (CR) rates in MEL 140 and MEL 200 were 16% and 29%, respectively (p=0.03).  There was no significant difference in (CR) + very good partial remission (VGPR), or overall response (CR + VGPR + PR) between MEL 140 and MEL 200.  Median follow up in surviving patients in MEL 140 and 200 was 7.6 and 25 months, respectively. Fifteen (24%) and 64 (25%) patients died in MEL 140 and MEL 200 groups, respectively, with >90% of deaths due to recurrent disease. Median PFS was 26.4 and 30.6 months in MEL 140 and MEL 200 groups, respectively (p=0.46).  Median OS was 38.4 and 93.0 months in MEL 140 and MEL 200 groups, respectively (p=0.02). However, there was no significant difference in median PFS (26 vs. 24.4 months) or median OS (38.6 vs. 62.2 months) in patients older than 65 between MEL 140 and MEL 200.  Similarly, there was no significant difference in median PFS (24.5 vs. 31.3 months) or median OS (32.1 months vs. 69.3 months) in patients with a serum Cr > 2 mg/d between MEL 140 and MEL 200.

Conclusion: The dose of melphalan can be safely reduced to 140 mg/m² in patients >65 or with renal insufficiency without adversely impacting the overall response rate or PFS.