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

Abstract

Melphalan at a dose of 200 mg/m2 is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m2 and melphalan 140 mg/m2 are equally effective and tolerable in clinically relevant patient subgroups we analyzed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, hematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 mg/m2 (n=245) and melphalan 200 mg/m2 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 mg/m2 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 mg/m2 versus melphalan 140 mg/m2: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favored melphalan 140 mg/m2 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 mg/m2 and melphalan 140 mg/m2 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favor the use of melphalan 200 mg/m2 or melphalan 140 mg/m2 for key transplant outcomes (NCT01362972).

Autologous peripheral blood stem cell transplantation in dialysis‐dependent multiple myeloma patients—DAUTOS Study of the Polish Myeloma Study Group

“…1,4,7,11,19,22 On the other hand, due to increased concentrations of melphalan and its antimyeloma effect, when patients overcome toxicity, one could expect a positive effect on the quality of response and prolongation of time to progression and death. 24,31,32 The positive effects in DD patients may result also from the correct qualification process by itself, because they are not dialysis-dependent multiple myeloma patients are treated with auto-PBSCT, but they are dialysis-dependent patients in whom due to generally good organ function (apart from renal failure) a low number of comorbidities, good performance status (in opposition to not eligible DD patients) and acceptablecompliance, the decision to undergo auto-PBSCT was made. These favourable factors, despite renal failure, are known to positively influence early outcomes following auto-PBSCT and likely increase the probability of PFS.…”

Female sex as an independent prognostic factor in the development of oral mucositis during autologous peripheral stem cell transplantation

“…In MM conditioning was administration of 140 mg/m 2 melphalan in 12 patients and 200 mg/m 2 in the rest of the patients. Treatment regimens according to the European Society for Blood and Marrow Transplantation (EBMT) recommendation 9 , 10 are summarized in Supplementary Tables S1 – S4 . None of the patients received cryotherapy.…”

Bortezomib consolidation following autologous transplant in younger and older patients with newly diagnosed multiple myeloma in two phase III trials

“…As noted above, age‐adjusted high‐dose MEL140 prior to ASCT is an option for older patients who may not tolerate the standard MEL200 . In our multivariate analysis, MEL200 prior to ASCT was not shown to be an independent prognostic variable for PFS or OS, despite the standard 200 mg/m 2 dose appearing to result in better outcomes on univariate analysis.…”