Bortezomib in Combination with Bendamustine and Prednisone in the Treatment of Patients with Refractory/Relapsed Multiple Myeloma.

Introduction: Bortezomib is a novel proteasome inhibitor that has shown important clinical efficacy either as a single agent or in combination with other cytostatic agents in relapsed/refractory multiple myeloma (MM). The combinated treatment of bortezomib with bendamustine and prednisone (BPV) was assessed to determine the efficacy and toxicity of this regiment in patients with advanced MM.

Methods: Between January 2005 and July 2007, 46 patients (median age 63; range 31–77 years) with relapsed or refractory MM (29 patients stage III a, 17 patients III b) were treated with bendamustine 60 (−80) mg/qm on day 1 and 2, bortezomib 1,3 mg/qm on day 1, 4, 8 and 11, and prednisone 100 mg on day 1, 2, 4, 8 and 11. Cycles were repeated every 21 days until maximum response or progressive disease. The time from first diagnosis ranged from 1 to 183 (median 36) months. The duration of the last remission before beginning the BPV-therapy was 6 (range 0–36) months. Previous therapy lines (median 2, range 1–6) included 18 × thalidomide, 10 × autologous PBSCT, and 9 × autologous/allogeneic PBSCT. 16 patients were refractory to the last treatment. 22 patients had preexistent severe thrombocytopenia, leukocytopenia or anemia (WHO grade 3 or 4). Response was assessed using EBMT criteria modified to include near complete remission (nCR) and very good partial remission (VGPR).

Results: 36 patients (78%) responded after at least one cycle of chemotherapy with 2 CR, 5 nCR, 6 VGPR, 15 PR and 8 MR. 4 patients had stable disease and 6 patients had a progress. With a median follow up of 13 months, EFS, and OS at twelve months for patients without severe haematological toxicities due to previous treatments (n=24) were 46% and 79%, respectively. Outcome for these patients was significantly better compared to patients with severe haematological toxicities (grade 3 or 4, n=22) where EFS, and OS were 10% and 22%, respectively (p<0,01). The median number of the BPV-treatment was 2 (1–7) cycles. 20 of 36 responding patients showed a rapid decrease of the myeloma protein and reached the best response after the first cycle and 12 after the second cycle. The regimen was well-tolerated with few significant side effects reported. New cytopenias occured infrequently (four patients had a thrombocytopenia grade 3, and two patients had a grade 4 thrombocytopenia). 1 patient had a moderate new polyneuropathy (grade 2).

Summary: These results indicate that the combination of bortezomib, bendamustine and prednisone is effective and well tolerated in a heavily pretreated population of patients with relapsed or refractory MM.