[Skip to Content]
[Skip to Content Landing]
Original Investigation
October 2018

Maintenance Treatment and Survival in Patients With Myeloma: A Systematic Review and Network Meta-analysis

Author Affiliations
  • 1Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy
  • 2Newcastle upon Tyne Hospitals Trust, United Kingdom
  • 3Hematology Department, IDIBAPS, Hospital Clinic, Barcelona, Spain
  • 4Department of Internal Medicine, University of Nebraska Medical Center, Omaha
  • 5Hematology Department, University Hospital Hôtel-Dieu, Nantes, France
  • 6The Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock
  • 7Hospital Universitario 12 de Octubre, Madrid, Spain. PETHEMA/Grupo Español de Mieloma
  • 8Hématologie and Inserm CIC 1082, Poitiers, France
  • 9Unit of Clinical Epidemiology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino and CPO Piemonte, Torino, Italy
  • 10Service d’Hématologie, Hôpital Haut-Lévêque, CHU Bordeaux, 33600 Pessac, France
  • 11Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom
  • 12Division of Hematology, AOU Policlinico-OVE, University of Catania, Catania, Italy
  • 13Institut d'Hématologie de Basse Normandie, University Hospital of Caen, Côte de Nacre, 14033 Caen Cedex 9, France
  • 14Università degli Studi di Perugia, Struttura Complessa Universitaria Oncoematologia - Azienda Ospedaliera Santa Maria di Terni, Italy
  • 15The Institute of Cancer Research, London, United Kingdom
  • 16Clinica di Ematologia, AOU Ospedali Riuniti di Ancona, Ancona, Italy
  • 17Department of Haematology, Alfred Health-Monash University, Melbourne, Australia
  • 18Department of Haematooncology, University Hospital Ostrava, Czech Republic and Faculty of Medicine, University of Ostrava, Czech Republic
  • 19Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
  • 20Hematology Department, IDIBAPS, Hospital Clinic, Barcelona, Spain
  • 21Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
  • 22Clínica Universidad de Navarra-CIMA, IDISNA, CIBERONC, Pamplona, Spain
  • 23Blood and Marrow Transplant Program, Department of Medicine, Roswell Park Comprehensive Cancer Center, State University at Buffalo, Buffalo, New York
  • 24Wilhelminen Cancer Research Institute, Vienna, Austria
  • 25University Hospital of Salamanca-Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain
  • 26Department of Hematology, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France
JAMA Oncol. 2018;4(10):1389-1397. doi:10.1001/jamaoncol.2018.2961
Key Points

Question  What is the current best maintenance approach in patients with myeloma?

Findings  This network meta-analysis included 11 trials and 8 treatments including a total of 5073 participants and found that 6 maintenance treatments prolonged progression-free survival vs no maintenance: lenalidomide-based regimens were identified as the most effective options. On overall survival analysis, lenalidomide alone was identified as the best option; similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups.

Meaning  By synthesizing the available evidence of novel agent-based maintenance in the last 20 years, lenalidomide maintenance can be currently considered the best treatment option.

Abstract

Importance  Several trials demonstrated the impact of novel agent-based maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current evidence demonstrating the superiority of one regimen over the other, owing to the lack of direct/indirect comparisons.

Objective  To analyze and compare the effectiveness of different maintenance regimens in NDMM via a network meta-analysis.

Data Sources  We performed 2 independent searches in PubMed and Cochrane databases, and then we identified all the records registered after 1999 and on or before November 20, 2017.

Study Selection  By blinded review, we identified prospective phase 3 randomized trials evaluating novel agent-based maintenance in patients with NDMM; the included studies compared at least 2 maintenance approaches; comparators included placebo and no maintenance. From 364 screened records, 11 studies were included.

Data Extraction and Synthesis  We followed (independent extraction) the guidelines provided by the PRISMA Report and the EQUATOR Network. The evidence was synthesized using a network meta-analysis (NMA). To allow comparison of all treatments, no maintenance was selected as common comparator and the effect of placebo was assumed to be the same as no treatment. The best option was identified by a Bayesian consistency model based on hazard ratio (HR), 95% credible interval (CrI), probability of being the best treatment (PbBT), and median ranking distribution (MedR).

Main Outcomes and Measures  Outcomes of interest were progression-free survival (PFS) and overall survival (OS).

Results  Eleven trials and 8 treatments including a total of 5073 participants were included. By PFS analysis, lenalidomide-based regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the most effective options (HR, 0.39 [95% CrI, 0.28-0.53] and 0.47 [95% CrI, 0.39-0.55], respectively; MedR, 1 and 2; overall PbBT, 74%). Four treatments (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone, thalidomide alone) showed an HR in favor of maintenance. By OS analysis, lenalidomide alone was identified as the best option (HR, 0.76; 95% CrI, 0.51-1.16; MedR, 2; PbBT, 38%), followed by bortezomib-thalidomide and bortezomib-prednisone. Similar features were noticed in the restricted network including transplant trials, in the sensitivity analysis, and in most of the prognostic subgroups.

Conclusions and Relevance  Based on PFS and OS results of this NMA, lenalidomide maintenance appears to be the best treatment option, by synthesizing the available evidence of novel agent-based maintenance in the past 20 years.

×