TY - JOUR
T1 - Primary therapy of Waldenström macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR)
T2 - Long-term results of a phase 2 study of the European Myeloma Network (EMN)
AU - Dimopoulos, Meletios A.
AU - Garćia-Sanz, Ramón
AU - Gavriatopoulou, Maria
AU - Morel, Pierre
AU - Kyrtsonis, Marie Christine
AU - Michalis, Eurydiki
AU - Kartasis, Zafiris
AU - Leleu, Xavier
AU - Palladini, Giovanni
AU - Tedeschi, Alessandra
AU - Gika, Dimitra
AU - Merlini, Giampaolo
AU - Kastritis, Efstathios
AU - Sonneveld, Pieter
PY - 2013/11/7
Y1 - 2013/11/7
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2013-05-503862
DO - 10.1182/blood-2013-05-503862
M3 - Article
C2 - 24004667
AN - SCOPUS:84888260930
VL - 122
SP - 3276
EP - 3282
JO - Blood
JF - Blood
SN - 0006-4971
IS - 19
ER -