Melphalan 140 mg/m2 or 200 mg/m2 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

Research output: Contribution to journalArticle

Abstract

Melphalan at a dose of 200 mg/m2 is standard conditioning prior to autologous hematopoietic stem cell transplantation for multiple mulholger, 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).

Details

Authors
  • Holger W. Auner
  • Simona Iacobelli
  • Giulia Sbianchi
  • Cora Knol-Bout
  • Didier Blaise
  • Nigel H. Russell
  • Jane F. Apperley
  • David Pohlreich
  • Paul V. Browne
  • Guido Kobbe
  • Cecilia Isaksson
  • Stig Lenhoff
  • Christof Scheid
  • Cyrille Touzeau
  • Esa Jantunen
  • Achilles Anagnostopoulos
  • Ibrahim Yakoub-Agha
  • Alina Tanase
  • Nicolaas Schaap
  • Wieslaw Wiktor-Jedrzejczak
  • And 5 others
  • Marta Krejci
  • Stefan O. Schönland
  • Curly Morris
  • Laurent Garderet
  • Nicolaus Kröger
External organisations
  • Imperial College London
  • University of Rome Tor Vergata
  • Institut Paoli-Calmettes
  • University of Nottingham
  • Charles University in Prague
  • Trinity College Dublin
  • Heinrich Heine University Düsseldorf
  • Umeå University
  • Skåne University Hospital
  • University of Cologne
  • Nantes University Hospital
  • Kuopio University Hospital
  • George Papanicolaou General Hospital
  • Lille University Hospital
  • Fundeni Clinical Institute
  • Radboud University Nijmegen
  • Medical University of Warsaw
  • University Hospital Brno
  • Heidelberg University
  • Queen's University Belfast
  • Hospital Saint-Antoine
  • University Medical Center Hamburg-Eppendorf
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)514-521
JournalHaematologica
Volume103
Issue number3
Publication statusPublished - 2018 Feb 28
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes