title: Response rate to the treatment of Waldenström macroglobulinemia: A meta-analysis of the results of clinical trials.
abstract: Waldenström macroglobulinemia (WM) is a malignant lymphoproliferative disorder characterized by the presence of a high level of serum monoclonal IgM and a lymphoplasmacytic infiltrate in the bone marrow. This meta-analysis sought to assess the effectiveness of the different treatments for WM tested in published trials using the response rate (RR) as the main outcome measure. Forty-six articles (1409 patients) identified were entered in a variable effects model meta-analysis of proportions (rates and sample sizes). A greater response to treatment was produced in patients treated with a combination of 2+ drugs (RR=73%; 95%CI: 62, 83; p<0.01) than in those receiving monotherapy with rituximab (RR=44%; 95%CI: 34, 55; p<0.01) or a purine analogue [61% (95%CI: 43, 78; p<0.01) for cladribine and 53% (95%CI: 34, 72; p<0.01) for fludarabine]. The combination rituximab+cladribine emerged as particularly effective (RR=87%; 95%CI: 78, 94; p<0.01), slightly more effective than rituximab+bortezomib/dexamethasone (RR=84%; 95%CI: 79, 88; p<0.01) and rituximab+cyclophosphamide/dexamethasone [RR=81% (95%CI: 72, 88; p<0.01)]. Our results are in overall agreement with treatment recommendations from the seventh International Workshops on WM. Our findings are limited by the fact that we could not analyze progression-free survival (PFS). More phase II/III trials are needed to corroborate promising recent findings with bendamustine and carfilzomib and further research are needed to standardize recommendations based on maximum treatment efficacy combined with lowest toxicity, differentiation between first vs second line treatment, or long-term follow up after treatment.
authors.affiliation: Research Institute of the Hospital 12 de Octubre ("i+12"), Madrid, Spain; GIDFYS, European University Miguel de Cervantes, Department of Health Sciences, Valladolid, Spain. Electronic address: asantos@uemc.es.
authors.forename: A
authors.initials: A
authors.lastname: Santos-Lozano
authors.affiliation: Faculty of Health Science, University of León, León, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Morales-Gonzalez
authors.affiliation: Research Institute of the Hospital 12 de Octubre ("i+12"), Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.affiliation: Laboratorio de Motricidad Humana, Escuela de Educación Física, Pontificia Universidad Católica de Valparaíso, Chile; Universidad Autónoma de Chile, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Cristi-Montero
authors.affiliation: Research Institute of the Hospital 12 de Octubre ("i+12"), Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Fiuza-Luces
authors.affiliation: Research Institute of the Hospital 12 de Octubre ("i+12"), Madrid, Spain; European University, Madrid, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Pareja-Galeano
authors.affiliation: Servicio de Hematología Hospital 12 de Octubre, Unidad CRIS, Universidad Complutense de Madrid, Departamento de Medicina, Spain; Hematological Cancer Unit, CNIO, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Martínez-López
authors.affiliation: Research Institute of the Hospital 12 de Octubre ("i+12"), Madrid, Spain; Department of Physiotherapy and Nursing, University of Zaragoza, Huesca, Spain; GENUD (Growth, Exercise, Nutrition and Development) Research Group, University of Zaragoza, Zaragoza, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Garatachea
authors.affiliation: Research Institute of the Hospital 12 de Octubre ("i+12"), Madrid, Spain; European University, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Lucia
mesh_terms: D004338:Drug Combinations; D006801:Humans; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D004338:Drug Combinations
keywords: Meta-analysis; Purine analogues; Rituximab; Waldeström disease