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Ferrata Storti Foundation
Haematologica 2019 Volume 104(11):2274-2282
Plasma Cell Disorders
Bortezomib-based induction followed by stem cell transplantation in light chain amyloidosis: results of the multicenter HOVON 104 trial
Monique C. Minnema,1 Kazem Nasserinejad,2 Bouke Hazenberg,3 Ute Hegenbart,4 Philip Vlummens,5 Paula F. Ypma,6 Nicolaus Kröger,7 Ka Lung Wu,8 Marie Jose Kersten,9 M. Ron Schaafsma,10 Sandra Croockewit,11 Esther de Waal,12 Sonja Zweegman,13 Lidwien Tick,14 Annemieke Broijl,15 Harry Koene,16 Gerard Bos,17 Pieter Sonneveld15 and Stefan Schönland4
1Department of Hematology, UMC Utrecht Cancer Center, Utrecht, the Netherlands; 2HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 3Department of Rheumatology & Clinical Immunology, University of Groningen Medical Center, Groningen, the Netherlands; 4Department of Hematology, Oncology and Rheumatology, Heidelberg University, Amyloidosis Center, Heidelberg, Germany; 5Department of Haematology, Ghent University, Gent, Belgium; 6Department of Hematology, HagaZiekenhuis, Den Haag, the Netherlands; 7Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 8Department of Hematology, ZNA Stuivenberg, Antwerp, Belgium; 9Department of Hematology, Academic Medical Center, Lymphoma and Myeloma Center, Amsterdam, the Netherlands; 10Department of Hematology, Medisch Spectrum Twente, Enschede, the Netherlands; 11Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; 12Department of Hematology, University of Groningen, Medical Center, Groningen, the Netherlands; 13Department of Hematology, VU University Medical Center, Amsterdam Cancer Center, Amsterdam, the Netherlands; 14Department of Internal Medicine, Maxima Medisch Centrum, Eindhoven, the Netherlands; 15Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 16Department of Hematology, St. Antonius Hospital, Nieuwegein, the Netherlands and 17Department of Hematology, Maastricht University Medical Center, Maastricht, the Netherlands
ABSTRACT
This prospective, multicenter, phase II study investigated the use of four cycles of bortezomib-dexamethasone induction treatment, fol- lowed by high-dose melphalan and autologous stem cell transplanta- tion (SCT) in patients with newly diagnosed light chain amyloidosis. The aim of the study was to improve the hematologic complete remission (CR) rate 6 months after SCT from 30% to 50%. Fifty patients were enrolled and 72% had two or more organs involved. The overall hematologic response rate after induction treatment was 80% including 20% CR and 38% very good partial remissions (VGPR). Fifteen patients did not proceed to SCT for various reasons but mostly treatment-related toxicity and disease-related organ damage and death (2 patients). Thirty-one patients received melpha- lan 200 mg/m2 and four patients a reduced dose because of renal function impairment. There were no deaths related to the transplantation procedure. Hematologic responses improved at 6 months after SCT to 86% with 46% CR and 26% VGPR. However, due to the high treatment discontinuation rate before transplantation the primary endpoint of the study was not met and the CR rate in the intention-to-treat analysis was 32%. Organ respons- es continued to improve after SCT. We confirm the high efficacy of borte- zomib-dexamethasone treatment in patients with AL amyloidosis. However, because of both treatment-related toxicity and disease character- istics, 30% of the patients could not proceed to SCT after induction treat- ment. (Trial registered at Dutch Trial Register identifier NTR3220).
Correspondence:
MONIQUE C. MINNEMA
m.c.minnema@umcutrecht.nl
Received: December 6, 2018. Accepted: March 18, 2019. Pre-published: March 28, 2019.
doi:10.3324/haematol.2018.213900
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/11/2274
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