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.

Blood and Marrow Transplant Program Department of Medicine Roswell Park Comprehensive Cancer Center State University at Buffalo Buffalo New York

Clinica di Ematologia AOU Ospedali Riuniti di Ancona Ancona Italy

Clínica Universidad de Navarra CIMA IDISNA CIBERONC Pamplona Spain

Clinical Trials Research Unit Leeds Institute of Clinical Trials Research University of Leeds Leeds United Kingdom

Department of Clinical Therapeutics National and Kapodistrian University of Athens School of Medicine Athens Greece

Department of Haematology Alfred Health Monash University Melbourne Australia

Department of Haematooncology University Hospital Ostrava Czech Republic and Faculty of Medicine University of Ostrava Czech Republic

Department of Hematology Erasmus Medical Center Rotterdam the Netherlands

Department of Hematology Institut Universitaire du Cancer Toulouse Oncopole Toulouse France

Department of Internal Medicine University of Nebraska Medical Center Omaha

Division of Hematology AOU Policlinico OVE University of Catania Catania Italy

Hématologie and Inserm CIC 1082 Poitiers France

Hematology Department IDIBAPS Hospital Clinic Barcelona Spain

Hematology Department University Hospital Hôtel Dieu Nantes France

Hospital Universitario 12 de Octubre Madrid Spain PETHEMA Grupo Español de Mieloma

Institut d'Hématologie de Basse Normandie University Hospital of Caen Côte de Nacre 14033 Caen Cedex 9 France

Myeloma Unit Division of Hematology University of Torino Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino Torino Italy

Newcastle upon Tyne Hospitals Trust United Kingdom

Service d'Hématologie Hôpital Haut Lévêque CHU Bordeaux 33600 Pessac France

The Institute of Cancer Research London United Kingdom

The Myeloma Institute University of Arkansas for Medical Sciences Little Rock

Unit of Clinical Epidemiology Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino and CPO Piemonte Torino Italy

Università degli Studi di Perugia Struttura Complessa Universitaria Oncoematologia Azienda Ospedaliera Santa Maria di Terni Italy

University Hospital of Salamanca Instituto de Investigación Biomédica de Salamanca Salamanca Spain

Wilhelminen Cancer Research Institute Vienna Austria

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Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

Lenalidomide Maintenance with or without Prednisone in Newly Diagnosed Myeloma Patients: A Pooled Analysis