Melphalan 140 mg/m2 or 200 mg/m2 for autologous trasnplantation 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
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CitationAuner, Holger W. Iacobelli, Simona. Sbianchi, Giulia. Knol-Bout, Cora. Blaise, Didier. Russell, Nigel H. Apperley, Jane F. Pohlreich, David. Browne, Paul V. Kobbe, Guido. Isaksson, Cecilia. Lenhoff, Stig. Scheid, Christof. Touzeau, Cyrille. Jantunen, Esa. Anagnostopoulos, Achilles. Yakoub-Agha, Ibrahim. Tanase, Alina. Schaap, Nicolaas. Wiktor-Jedrzejczak, Wieslaw. et al.. (2018). Melphalan 140 mg/m2 or 200 mg/m2 for autologous trasnplantation 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. HAEMATOLOGICA, 103 (3) , 514-521. 10.3324/haematol.2017.181339.
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 seriesof 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 melphalan200 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).