title: BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years.
abstract: In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone, and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenström macroglobulinemia (WM), most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m2IV on days 1, 4, 8, and 11), followed by weekly IV bortezomib (1.6 mg/m2on days 1, 8, 15, and 22) for 4 additional 35-day cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m2) on cycles 2 and 5, for a total treatment duration of 23 weeks. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response). After a minimum follow-up of 6 years, median progression-free survival was 43 months and median duration of response for patients with at least partial response was 64.5 months. Overall survival at 7 years was 66%. No patient had developed secondary myelodysplasia, whereas transformation to high-grade lymphoma occurred in 3 patients who had received chemoimmunotherapy after BDR. Thus, BDR is a very active, fixed-duration, chemotherapy-free regimen, inducing durable responses and with a favorable long-term toxicity profile (www.ClinicalTrials.gov #NCT00981708).
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.affiliation: Hospital de Universitario de Salamanca, Salamanca, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Schaffner, Lens Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.affiliation: Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Kyrtsonis
authors.affiliation: Hematology Department, Gennimatas General Hospital, Athens, Greece.
authors.forename: Eurydiki
authors.initials: E
authors.lastname: Michalis
authors.affiliation: General Hospital of Chalkida, Chalkida, Greece.
authors.forename: Zafiris
authors.initials: Z
authors.lastname: Kartasis
authors.affiliation: Service d'Hématologie et de Thérapie Cellulaire Hôpital La Miletrie, CHU Poitiers, Poitiers, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.affiliation: Policlinico San Matteo, University of Pavia, Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.affiliation: Dirigente Medico Dipartimento di Oncologia ed Ematologia Struttura Complessa di Ematologia, Ospedale Niguarda Ca' Granda, Milan, Italy; and.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gika
authors.affiliation: Policlinico San Matteo, University of Pavia, Pavia, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.affiliation: Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
authors.affiliation: Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069286:Bortezomib / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D057194:Intention to Treat Analysis / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D000069283:Rituximab / Q000627:therapeutic use*; D016019:Survival Analysis; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D007075:Immunoglobulin M; D000069283:Rituximab; D000069286:Bortezomib; D003907:Dexamethasone