Page 159 - 2019_11 Resto del Mondo-web

Plasma Cell Disorders
Phase II study of carfilzomib, thalidomide, and low-dose dexamethasone as induction and consolidation in newly diagnosed, transplant eligible patients with multiple myeloma;
the Carthadex trial
Ferrata Storti Foundation
Haematologica 2019 Volume 104(11):2265-2273
Ruth Wester,1 Bronno van der Holt,2 Emelie Asselbergs,1 Sonja Zweegman,3 Marie Jose Kersten,2 Edo Vellenga,4 Marinus van Marwijk Kooy,5 Okke de Weerdt,6 Monique Minnema,7 Sarah Lonergan,1 Antonio Palumbo,8 Henk Lokhorst,3 Annemiek Broijl1 and Pieter Sonneveld1
1Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 2HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; 3Department of Hematology, Amsterdam UMC, Amsterdam, the Netherlands; 4Department of Hematology, University Medical Center Groningen, University of Groningen, the Netherlands; 5Department of Hematology, Isala Clinics, Zwolle, the Netherlands; 6Department of Internal Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands; 7Department of Hematology, UMC Utrecht Cancer Center, Utrecht, the Netherlands and 8Department of Hematology, University of Torino, Torino, Italy
ABSTRACT
This is a phase II dose escalation trial of carfilzomib in combination with thalidomide and dexamethasone for induction and consoli- dation in transplant-eligible patients with newly diagnosed multi- ple myeloma (NDMM). The results of four dose levels are reported. Induction therapy consisted of four cycles of carfilzomib 20/27 mg/m2 (n=50), 20/36 mg/m2 (n=20), 20/45 mg/m2 (n=21), and 20/56 mg/m2 (n=20) on days 1, 2, 8, 9, 15, 16 of a 28-day cycle; thalidomide 200 mg on day 1 through 28 and dexamethasone 40 mg weekly. Induction therapy was followed by high-dose melphalan and autologous stem cell trans- plantation and consolidation therapy with four cycles of carfilzomib, thalidomide and dexamethasone in the same schedule except a lower dose of thalidomide (50 mg). Very good partial response rate or better and complete response rate or better after induction therapy were 65% and 18%, respectively, increasing to 86% and 63%, respectively, after consolidation therapy. In all cohorts combined, after a median follow up of 58.7 months, median progression-free survival was 58 months (95%CI: 45-67 months). Median overall survival was 83 months (95%CI: 83 months-not reached). Grade 3/4 adverse events consisted mainly of infections, respiratory disorders, skin and vascular disorders in 11%, 8%, 9%, and 9%, respectively. Grade 3 polyneuropathy was only reported in one patient. Cardiac events were limited: grade 3/4 in 5% of patients. Carfilzomib, thalidomide and dexamethasone as induction and consoli- dation treatment after high-dose melphalan and autologous stem cell transplantation is highly efficacious and safe in transplant-eligible patients with NDMM. This study was registered as #NTR2422 at http://www.trialregister.nl
Introduction
Survival rates in patients with multiple myeloma (MM) have significantly improved during the last decades. However, eventually the majority of patients progress and the need for new therapeutic approaches remains. In transplant-eli- gible patients with newly diagnosed multiple myeloma (NDMM), depth of
Correspondence:
RUTH WESTER
r.wester@erasmusmc.nl.
Received: September 2, 2018. Accepted: March 28, 2019. Pre-published: April 4, 2019.
doi:10.3324/haematol.2018.205476
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/11/2265
©2019 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 | 2019; 104(11)
2265
ARTICLE