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

Abstract

Key Points• BDR is a chemotherapy-free, non-stem-cell-toxic regimen associated with high response rates and long-term remissions.• The long-term safety profile of BDR is favorable, with high probability of response to reintroduction of rituximabbased regimens at relapse.In this phase 2 multicenter trial, we evaluated the efficacy of the combination of bortezomib, dexamethasone, and rituximab (BDR) in 59 previously untreated symptomatic patients with Waldenström macroglobulinemia (WM), most of which were of advanced age and with adverse prognostic factors. BDR consisted of a single 21-day cycle of bortezomib alone (1.3 mg/m 2 IV on days 1, 4, 8, and 11), followed by weekly IV bortezomib (1.6 mg/m 2 on days 1, 8, 15, and 22) for 4 additional 35-day cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m 2 ) on cycles 2 and 5, for a total treatment duration of 23 weeks. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response). After a minimum follow-up of 6 years, median progression-free survival was 43 months and median duration of response for patients with at least partial response was 64.5 months. Overall survival at 7 years was 66%. No patient had developed secondary myelodysplasia, whereas transformation to high-grade lymphoma occurred in 3 patients who had received chemoimmunotherapy after BDR. Thus, BDR is a very active, fixedduration, chemotherapy-free regimen, inducing durable responses and with a favorable long-term toxicity profile (www.

How I treat Waldenström macroglobulinemia

“…Bortezomib, which has shown activity in several phase 2 studies, either alone or in combination with rituximab (VR or BDR) in either newly diagnosed or relapsed patients, [48][49][50][51] does not cause IgM flare and can rapidly reduce IgM levels, but marrow clearance may lag behind when used alone. 52 Today, bortezomib is administered subcutaneously and in weekly intervals 49,50,53 to reduce neurotoxicity.…”

“…These fixed-duration alkylator-free regimens, even without maintenance, offer prolonged progression free survival (PFS). 48,54 A randomized prospective study (ECWM-1) comparing DRC vs DRC with bortezomib in previously untreated symptomatic patients has completed accrual. The nonneurotoxic proteasome inhibitor carfilzomib has been tested in combination with rituximab in a small trial, but carfilzomib may be associated with a risk for cardiotoxicity.…”

Waldenström macroglobulinemia: 2019 update on diagnosis, risk stratification, and management

“…No patient required plasma exchange for flare. The response rate was 85%, the median PFS was 42 months, and the 3‐year OS was 81% . Peripheral neuropathy was seen in 46% .…”

How we manage patients with Waldenström macroglobulinaemia

“…In the recent analysis of the phase 2 study with newly diagnosed patients (with advanced age and adverse prognostic factors), MRR was 68%, and median PFS was 43 months. Time to next treatment was 73 months (Gavriatopoulou et al , ).…”