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
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,
Marta Krejci,
Stefan O. Schönland,
Curly Morris,
Laurent Garderet,
Nicolaus Kröger
Affiliations
Holger W. Auner
Department of Medicine, Imperial College London, UK
Simona Iacobelli
Department of Biology, Tor Vergata University of Rome, Italy
Giulia Sbianchi
Department of Biology, Tor Vergata University of Rome, Italy
Cora Knol-Bout
EBMT Data Office, Leiden, the Netherlands
Didier Blaise
Institut Paoli Calmettes, Marseille, France
Nigel H. Russell
Nottingham University, UK
Jane F. Apperley
Department of Medicine, Imperial College London, UK
David Pohlreich
Charles University Hospital, Prague, Czech Republic
Paul V. Browne
St. James’s Hospital, Trinity College Dublin, Ireland
Guido Kobbe
Heinrich Heine Universität, Düsseldorf, Germany
Cecilia Isaksson
Umeå University Hospital, Sweden
Stig Lenhoff
Skåne University Hospital, Lund, Sweden
Christof Scheid
University of Cologne, Germany
Cyrille Touzeau
CHU Nantes, France
Esa Jantunen
Kuopio University Hospital, Finland
Achilles Anagnostopoulos
George Papanicolaou General Hospital, Thessaloniki, Greece
Ibrahim Yakoub-Agha
CHU de Lille, LIRIC, INSERM U995, France
Alina Tanase
Fundeni Clinical Institute, Bucharest, Romania
Nicolaas Schaap
Radboud University Medical Centre, Nijmegen, the Netherlands
Wieslaw Wiktor-Jedrzejczak
Medical University, Warsaw, Poland
Marta Krejci
University Hospital Brno, Czech Republic
Stefan O. Schönland
University of Heidelberg, Germany
Curly Morris
Queens University of Belfast, Northern Ireland
Laurent Garderet
Hôpital Saint-Antoine, Paris, France
Nicolaus Kröger
University Hospital Hamburg-Eppendorf, Hamburg, Germany
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).
