Efficacy and tolerability of bendamustine, bortezomib and dexamethasone in patients with relapsed-refractory multiple myeloma: a phase II study

Abstract

Bendamustine demonstrated synergistic efficacy with bortezomib against multiple myeloma (MM) cells in vitro and seems an effective treatment for relapsed-refractory MM (rrMM). This phase II study evaluated bendamustine plus bortezomib and dexamethasone (BVD) administered over six 28-day cycles and then every 56 days for six further cycles in patients with rrMM treated with ⩽4 prior therapies and not refractory to bortezomib. The primary study end point was the overall response rate after four cycles. In total, 75 patients were enrolled, of median age 68 years. All patients had received targeted agents, 83% had 1–2 prior therapies and 33% were refractory to the last treatment. The response rate⩾partial response (PR) was 71.5% (16% complete response, 18.5% very good PR, 37% partial remission). At 12 months of follow-up, median time-to-progression (TTP) was 16.5 months and 1-year overall survival was 78%. According to Cox regression analysis, only prior therapy with bortezomib plus lenalidomide significantly reduced TTP (9 vs 17 months; hazard ratio=4.5; P=0.005). The main severe side effects were thrombocytopenia (30.5%), neutropenia (18.5%), infections (12%), neuropathy (8%) and gastrointestinal and cardiovascular events (both 6.5%). The BVD regimen is feasible, effective and well-tolerated in difficult-to-treat patients with rrMM.

Bendamustine in heavily pre-treated patients with relapsed or refractory multiple myeloma

“…ORR was 67 % (CR 10.9 %, VGPR 16.5 %, PR 39.7 %), and median OS was estimated at 23 months. A response rate of 71.5 % (16 % CR, 18.5 % VGPR, 37 % PR) in 75 patients who had a median of one line of previous therapy was reported by Offidani et al (2013) in a phase II study with the BVD regimen.…”

“…Few severe hematological side effects were reported (20.5 % neutropenia, 9.5 % thrombocytopenia, 5.5 % anemia) (Rodon et al 2015). In the study conducted by Offidani et al (2013) with the BVD regimen, common severe adverse events were thrombocytopenia (30.5 %), neutropenia (18.5 %), infections (12 %) and neuropathy (8 %).…”

Multiple myeloma: patient outcomes in real‐world practice

“…Given the availability of agents that are effective in relapsed and refractory MM (Singhal et al , 1999; Richardson et al , 2005; Dimopoulos et al , 2007; Weber et al , 2007; Offidani et al , 2013; San Miguel et al , 2013; San‐Miguel et al , 2014; Stewart et al , 2015), it is perhaps surprising that relatively few patients receive multiple lines of therapy. About a quarter of patients completed fourth‐line treatment as planned, and 38% of patients ended fourth‐line treatment in remission, suggesting that patients do benefit from receiving treatment at this later stage; however, very few reach fifth‐line treatment (1%).…”

Therapy for Relapsed Multiple Myeloma

“…It has single agent activity in multiple myeloma, but it is generally used in combination with dexamethasone and IMiDs 97,98 or bortezomib 99–102 for therapy for relapsed disease. The major adverse effects of bendamustine are fatigue, rash, headache, constipation, and cytopenias.…”