Page 154 - Haematologica3

Correspondence:
holger.auner04@imperial.ac.uk
Received: September 29, 2017. Accepted: December 1, 2017. Pre-published: December 7, 2017.
doi:10.3324/haematol.2017.181339
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/3/514
©2018 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
Haematologica 2018 Volume 103(3):514-521
Holger W. Auner,1 Simona Iacobelli2, Giulia Sbianchi,2 Cora Knol-Bout,3 Didier Blaise,4 Nigel H. Russell,5 Jane F. Apperley,1 David Pohlreich,6
Paul V. Browne,7 Guido Kobbe,8 Cecilia Isaksson,9 Stig Lenhoff,10 Christof Scheid,11 Cyrille Touzeau,12 Esa Jantunen,13 Achilles Anagnostopoulos,14 Ibrahim Yakoub-Agha,15 Alina Tanase,16 Nicolaas Schaap,17
Ferrata Storti Foundation
Plasma Cell Disorders
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
Wieslaw Wiktor-Jedrzejczak,18 Marta Krejci,19 Stefan O. Schönland,20 Curly Morris,21 Laurent Garderet22 and Nicolaus Kröger23
1Department of Medicine, Imperial College London, UK; 2Department of Biology, Tor Vergata University of Rome, Italy; 3EBMT Data Office, Leiden, the Netherlands; 4Institut Paoli Calmettes, Marseille, France; 5Nottingham University, UK; 6Charles University Hospital, Prague, Czech Republic; 7St. James's Hospital, Trinity College Dublin, Ireland; 8Heinrich Heine Universität, Düsseldorf, Germany; 9Umeå University Hospital, Sweden; 10Skåne University Hospital, Lund, Sweden; 11University of Cologne, Germany; 12CHU Nantes, France; 13Kuopio University Hospital, Finland; 14George Papanicolaou General Hospital, Thessaloniki, Greece; 15CHU de Lille, LIRIC, INSERM U995, France; 16Fundeni Clinical Institute, Bucharest, Romania; 17Radboud University Medical Centre, Nijmegen, the Netherlands; 18Medical University, Warsaw, Poland; 19University Hospital Brno, Czech Republic; 20University of Heidelberg, Germany; 21Queens University of Belfast, Northern Ireland; 22Hôpital Saint-Antoine, Paris, France and 23University Hospital Hamburg-Eppendorf, Hamburg, Germany
ABSTRACT
Melphalan at a dose of 200 mg/m2 is standard conditioning prior to autologous hematopoietic stem cell transplantation for mul-
2
tiple myeloma, but a dose of 140 mg/m 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 ana- lyzed 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 sur- vival, 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 mel- phalan 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 signif- icantly favored melphalan 140 mg/m2 for overall survival (adjusted haz- ard 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 sig- nificant 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 melpha- lan 140 mg/m2 for key transplant outcomes (NCT01362972).
514
haematologica | 2018; 103(3)
ARTICLE