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/m2 days 1, 8, 15, and 22) every 35 days for 4 additional cycles, followed by IV dexamethasone (40 mg) and IV rituximab (375 mg/m2) 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 was42months, 3-year durationof 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.

dx.doi.org/10.1182/blood-2013-05-503862, hdl.handle.net/1765/63647
Blood
Department of Hematology

Dimopoulos, M.A, Garcia-Sanz, R, Gavriatopoulou, M, Morel, P, Kyrtsonis, M.-C, Michalis, L.K, … Sonneveld, P. (2013). Primary therapy of Waldenström 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). Blood, 122(19), 3276–3282. doi:10.1182/blood-2013-05-503862