title: Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN).
abstract: In this phase 2 multicenter trial, we evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) combination in previously untreated symptomatic patients with Waldenström macroglobulinemia (WM). To prevent immunoglobulin M (IgM) "flare," single agent bortezomib (1.3 mg/m(2) IV days 1, 4, 8, and 11; 21-day cycle), was followed by weekly IV bortezomib (1.6 mg/m(2) days 1, 8, 15, and 22) every 35 days for 4 additional cycles, followed by IV dexamethasone (40 mg) and IV rituximab (375 mg/m(2)) in cycles 2 and 5. Fifty-nine patients were treated; 45.5% and 40% were high and intermediate risk per the International Prognostic Scoring System for WM. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response [PR]). In 11% of patients, an increase of IgM ≥25% was observed after rituximab; no patient required plasmapheresis. After a minimum follow-up of 32 months, median progression-free survival was 42 months, 3-year duration of response for patients with ≥PR was 70%, and 3-year survival was 81%. Peripheral neuropathy occurred in 46% (grade ≥3 in 7%); only 8% discontinued bortezomib due to neuropathy. BDR is rapidly acting, well tolerated, and nonmyelotoxic, inducing durable responses in previously untreated WM.
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece;
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.forename: Pierre
authors.initials: P
authors.lastname: Morel
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Kyrtsonis
authors.forename: Eurydiki
authors.initials: E
authors.lastname: Michalis
authors.forename: Zafiris
authors.initials: Z
authors.lastname: Kartasis
authors.forename: Xavier
authors.initials: X
authors.lastname: Leleu
authors.forename: Giovanni
authors.initials: G
authors.lastname: Palladini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tedeschi
authors.forename: Dimitra
authors.initials: D
authors.lastname: Gika
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000473:pathology; D011719:Pyrazines / Q000008:administration & dosage; D000069283:Rituximab; D016019:Survival Analysis; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D007075:Immunoglobulin M; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib; D003907:Dexamethasone