Effect of melphalan 140 mg/m² vs 200 mg/m² on toxicities and outcomes in multiple myeloma patients undergoing single autologous stem cell transplantation—a single center experience

Abstract

Although melphalan at a dose of 140 mg/m(2) (MEL140) is an acceptable conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients, very few studies compared it to the most commonly used dose of 200 mg/m(2) (MEL200). A retrospective review of records of MM patients (2001-2010) identified 33 patients who received MEL140 and 96 patients who received MEL200. As expected, significantly higher percentage of patients in the MEL140 arm were >65 years or had cardiac ejection fraction <50%, had Karnofsky score <80, or had creatinine >2 at the time of ASCT (P≤.01). There were no significant differences in incidence of treatment related mortality and morbidity. At a median follow-up of 74 months from ASCT, there were no significant differences in relapse free survival (RFS) and overall survival (OS) between the two groups. Similar proportion had myeloma status improve to ≥VGPR at 3 months post-ASCT. Usage of post-ASCT maintenance was similar. In multivariate cox proportional hazards model, only disease status of ≥VGPR at the time of ASCT significantly improved RFS (P=.024), but not OS (P=.104). In conclusion, MM patients who received MEL140 had similar long-term outcomes to MEL200 patients despite their older age and co-morbidities.

Melphalan 140 mg/m 2 or 200 mg/m 2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

“…While some studies have suggested that older age and renal impairment can be linked to excess toxicity with Mel200, others have not reported such an association. 19 , 20 , 22 – 24 , 26 , 32 – 34 The results of this study support the notion that older age and impaired renal function do not favor the use of a lower melphalan dose with regards to non-relapse mortality, hematopoietic recovery, or second primary malignancy rate. Moreover, we found no interaction of Karnofsky performance score with melphalan dose.…”

“… 17 – 19 Consequently, a dose of 140 mg/m 2 (Mel140) is widely used in clinical practice in older patients and in patients with renal impairment. 20 – 25 However, Mel140 was associated with inferior response or survival rates compared to Mel200 in two very recent studies. 24 , 26 It therefore remains to be determined whether Mel140 and Mel200 are equally effective and tolerable across subgroups of patients.…”

A Phase 1 Study of Intravenous Busulfan as a Conditioning Regimen for Multiple Myeloma

“…Even though overall response rates and PFS were similar between the two groups, the rates of complete responses and overall survival were significantly lower for the MEL 140 group 5 . However, a similar study by Katragadda et al on 33 patients with MEL 140 and 96 patients with MEL 200 showed no significant difference in treatment-related mortality, relapse-free survival or overall survival between the groups 6 .…”

Full or intensity‐reduced high‐dose melphalan and single or double autologous stem cell transplant with or without bortezomib consolidation in patients with newly diagnosed multiple myeloma

“…22,23 Due to concerns about increased toxicity, older patients, however, may receive intensityreduced high-dose melphalan. 24,25 Studies have shown good results with two courses of 100 mg/mg² melphalan 26 as well as with one or two courses of 140 mg/m² melphalan. 27,28 However, it remains to be determined whether age-adjusted and full high-dose melphalan are all in all equally effective, 29 or whether MEL200 is generally more advantageous.…”