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)

Abstract

Key Points• BDR is an active regimen and induces long-lasting responses in patients with newly diagnosed WM.• Induction with single-agent bortezomib may be effective in preventing complications of hyperviscosity or rituximabinduced IgM flare.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.

BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years

“…Their characteristics, response rates and toxicity were reported previously. 14 Briefly, most were of advanced age (61% were .65 years) with adverse prognostic factors (hemoglobin ,11.5 g/dL in 82% and b2-microglobulin $3 mg/dL in 64%), so that 45.5% and 40% were rated as high and intermediate risk per the International Prognostic Scoring System for WM (IPSSWM). 3 On intent to treat, 85% of the patients responded (3% complete response [CR], 7% very good partial response [VGPR], 58% partial response [PR], and 17% minor response [MR]), for a major response rate ($PR) of 68%.…”

Lung consolidation as a rare presentation of lymphoplasmacytic lymphoma with extramedullary Waldenström’s macroglobulinemia

“…Patient with symptomatic hyperviscosity, cold agglutinemia, or cryoglobulinemia can be treated initially with plasmapheresis then induction with bortezomib followed by rituximab [18]. Patients with paraprotein-related nephropathy can be treated with plasmapheresis initially then with rituximab [19].…”

Cost-effectiveness analysis of ibrutinib in patients with Waldenström macroglobulinemia in Italy

“…Clinical input data (efficacy and safety), treatment dosing schedules, overall population mortality were used to populate the model and derived respectively from global trials (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) as well as published literature [1,16,[18][19][20][21][22][23][24]. Comparative efficacy for ibrutinib vs. CTP was derived from a multivariate Cox proportional hazard model performed to estimate the hazard ratio (HR) of the PFS for ibrutinib vs. CTP [1,16,[18][19][20][21][22][23][24].…”

“…Comparative efficacy for ibrutinib vs. CTP was derived from a multivariate Cox proportional hazard model performed to estimate the hazard ratio (HR) of the PFS for ibrutinib vs. CTP [1,16,[18][19][20][21][22][23][24]. Missing characteristics data were imputed to ensure sufficient sample size.…”

“…The aim of this study is to estimate, from the Italian National Health System (NHS) perspective, the incremental cost-effectiveness ratio (ICER) of ibrutinib in relapsing/ refractory (R/R) WM, compared with the current therapeutic pathways (CTP) applied to WM: fludarabine + cyclophosphamide + rituximab (FCR), bortezomib + rituximab (BOR), rituximab + cyclophosphamide + doxorubicin + vincristine + prednisone (RCHOP), bortezomib + dexamethasone + rituximab (BDR), dexamethasone + rituximab + cyclophosphamide (DRC), and bendamustine/rituximab (BR) [1,[18][19][20][21][22][23].…”