Page 180 - 2019_05-HaematologicaMondo-web

Ferrata Storti Foundation
Haematologica 2018 Volume 104(5):1026-1035
Plasma Cell Disorders
Efficacy of first-line treatments for multiple myeloma patients not eligible for stem cell transplantation: a network meta-analysis
Hedwig M. Blommestein,1,2* Chrissy H.Y. van Beurden-Tan,3* Margreet G. Franken,1 Carin A. Uyl-de Groot,1,2 Pieter Sonneveld3 and Sonja Zweegman4
Decision making for patients with multiple myeloma (MM) not transplant eligible (NTE) is complicated by a lack of head-to- head comparisons of standards of care, the increase in the choice of treatment modalities, and the promising results that are rapidly evolv- ing from studies with novel regimens. To support evidence-based deci- sion making, we performed a network meta-analysis for NTE MM patients that synthesizes direct and indirect evidence and enables a com- parison of all treatments. Relevant randomized clinical trials were iden- tified by a systematic literature review in EMBASE®, MEDLINE®, MEDLINE®-in-Process and the Cochrane Central Register of Controlled Trials for January 1999 to March 2016. Efficacy outcomes [i.e. the hazard ratio (HR) and 95% confidence interval (95%CI) for progression-free sur- vival] were extracted and synthesized in a random effects network-meta analysis. In total, 24 studies were identified including 21 treatments. According to the network-meta analysis, the HR for progression-free survival was favorable for all NTE MM treatments compared to dexam- ethasone (HR: 0.19-0.90). Daratumumab-bortezomib-melphalan-pred- nisone and bortezomib-melphalan-prednisone-thalidomide with borte- zomib-thalidomide maintenance were identified as the most effective treatments (HR: 0.19, 95%CI: 0.08-0.45 and HR: 0.22, 95%CI: 0.10-0.51, respectively). HR and 95%CI for currently recommended treatments, bortezomib-lenalidomide-dexamethasone, bortezomib-melphalan- prednisone, and lenalidomide-dexamethasone compared to dexametha- sone, were 0.31 (0.16-0.59), 0.39 (0.20-0.75), and 0.44 (0.29-0.65), respec- tively. In addition to identifying the most effective treatment options, we illustrate the additional value and evidence of network meta-analysis in clinical practice. In the current treatment landscape, the results of net- work meta-analysis may support evidence-based decisions and ultimate- ly help to optimize treatment and outcomes of NTE MM patients.
Introduction
Multiple myeloma (MM) is a hematologic disease characterized by the prolifer- ation of malignant plasma cells, causing disease-related symptoms such as anemia, hypercalcemia, renal and bone disease. The age-standardized incidence rate is 4.5 per 100,000.1 Incidence increases with age and two-thirds of the patients diagnosed with MM are over 65 years of age.2 The treatment armamentarium has been great- ly increased in the last decade, with novel proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies now being incor- porated in first-line treatment regimens, which have considerably improved pro- gression-free survival (PFS) and overall survival (OS) of MM. Given the median age
*HB and CvBT contributed equally to this work
1Erasmus School of Health Policy & Management, Institute for Medical Technology Assessment, Erasmus University Rotterdam; 2Comprehensive Cancer Organisation, Utrecht; 3Erasmus MC Cancer Institute, Rotterdam and 4Department of Hematology, Amsterdam UMC, the Netherlands
ABSTRACT
Correspondence:
HEDWIG M. BLOMMESTEIN blommestein@eshpm.eur.nl
Received: September 14, 2018. Accepted: January 2, 2019. Pre-published: January 3, 2019.
doi:10.3324/haematol.2018.206912
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/5/1026
©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.
1026
haematologica | 2019; 104(5)
ARTICLE