Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia

Abstract

This study aimed to determine the activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenströ m Macroglobulinemia (WM). Patients with no prior therapy and symptomatic disease were eligible. Patients received bortezomib IV weekly at 1.6 mg/m 2 on days 1, 8, 15, q 28 days 3 6 cycles, and rituximab 375 mg/m 2 weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response (MR). Twenty-six patients were treated. At least MR was observed in 23/26 patients (88%) (95% CI: 70-98%) with 1 complete response (4%), 1 near-complete response (4%), 15 partial remission (58%), and 6 MR (23%). Using IgM response evaluated by nephlometry, all 26 patients (100%) achieved at least MR or better. The median time to progression has not been reached, with an estimated 1-year event free rate of 79% (95% CI: 53, 91%). Common grade 3 and 4 therapy related adverse events included reversible neutropenia in 12%, anemia in 8%, and thrombocytopenia in 8%. No grade 3 or 4 neuropathy occurred. The combination of weekly bortezomib and rituximab exhibited significant activity and minimal neurological toxicity in patients with untreated WM. Am. J. Hematol. 85:670-674, 2010. V

Simultaneous Presentation of Waldenstr^|^ouml;m Macroglobulinemia and Multiple Myeloma: Multidisciplinary Diagnosis, Treatment and 30-Month Follow-up

“…Nevertheless, the efficacy of therapy was good and an acceptable control of both WM and MM was achieved. Indeed, the combination of weekly bortezomib and rituximab exhibited significant activity in untreated patients with WM, 36 and the association of bortezomib and dexamethasone has been employed as first line therapy in patients with MM. 37,38 Therefore, we used a hybrid therapy schedule in an attempt to control both WM and MM.…”

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].…”

“…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].…”

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique

“…Rituximab, 7 chlorambucil, 8 alkylating agent combinations, 9 R-CHOP (rituximab, CY, doxorubicin (hydroxydaunorubicin), VCR (Oncovin) and prednisone) 10,11 and purine nucleoside analogs 12,13 have all produced high response rates, and many of the responses are durable. Recently, bortezomib 14,15 and bendamustine 16 have both been shown to be highly active in the management of Waldenströ m macroglobulinemia. Investigations into the use of the mTOR inhibitor everolimus 17 have shown it to be useful in heavily pretreated Waldenströ m macroglobulinemia.…”