Auner, 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 ORCID: 0000-0003-0275-2575, Jantunen, Esa, Anagnostopoulos, Achilles ORCID: 0000-0003-4384-9031, Yakoub-Agha, Ibrahim ORCID: 0000-0003-4524-8782, Tanase, Alina, Schaap, Nicolaas ORCID: 0000-0001-7696-4752, Wiktor-Jedrzejczak, Wieslaw, Krejci, Marta, Schoenland, Stefan O., Morris, Curly, Garderet, Laurent and Kroeger, Nicolaus (2018). 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. Haematologica, 103 (3). S. 514 - 522. PAVIA: FERRATA STORTI FOUNDATION. ISSN 0390-6078

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Abstract

Melphalan at a dose of 200 mg/m(2) is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple myeloma, but a dose of 140 mg/m(2) is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine whether melphalan 200 mg/m(2) and melphalan 140 mg/m(2) 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/m(2) (n=245) and melphalan 200 mg/m(2) (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/m(2) in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 mg/m(2) versus melphalan 140 mg/m(2): 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favored melphalan 140 mg/m(2) 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/m(2) and melphalan 140 mg/m(2) 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/m(2) or melphalan 140 mg/m(2) for key transplant outcomes (NCT01362972).

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Auner, Holger W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Iacobelli, SimonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sbianchi, GiuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knol-Bout, CoraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blaise, DidierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Russell, Nigel H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Apperley, Jane F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pohlreich, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Browne, Paul V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kobbe, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isaksson, CeciliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lenhoff, StigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheid, ChristofUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Touzeau, CyrilleUNSPECIFIEDorcid.org/0000-0003-0275-2575UNSPECIFIED
Jantunen, EsaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anagnostopoulos, AchillesUNSPECIFIEDorcid.org/0000-0003-4384-9031UNSPECIFIED
Yakoub-Agha, IbrahimUNSPECIFIEDorcid.org/0000-0003-4524-8782UNSPECIFIED
Tanase, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaap, NicolaasUNSPECIFIEDorcid.org/0000-0001-7696-4752UNSPECIFIED
Wiktor-Jedrzejczak, WieslawUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krejci, MartaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoenland, Stefan O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morris, CurlyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garderet, LaurentUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroeger, NicolausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-195446
DOI: 10.3324/haematol.2017.181339
Journal or Publication Title: Haematologica
Volume: 103
Number: 3
Page Range: S. 514 - 522
Date: 2018
Publisher: FERRATA STORTI FOUNDATION
Place of Publication: PAVIA
ISSN: 0390-6078
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STEM-CELL TRANSPLANTATION; HIGH-DOSE MELPHALAN; DIAGNOSED MULTIPLE-MYELOMA; ELDERLY-PATIENTS; RANDOMIZED-TRIAL; CONDITIONING REGIMEN; INTERGROUPE FRANCOPHONE; MARROW-TRANSPLANTATION; BONE-MARROW; CHEMOTHERAPYMultiple languages
HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19544

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