Clinical Efficacy of VEL-CTD (Bortezomib, Cyclophosphamide, Thalidomide, and Dexamethasone) Regimen in Patients with Relapsed or Refractory Multiple Myeloma: A Phase II Study

BACKGROUND: Recent studies demonstrates that the combination of bortezomib and several chemotherapeutic agents may have significant activity in myeloma. In this study, we assessed the efficacy and safety of the combination with bortezomib, cyclophosphamide, thalidomide, and dexamethasone (vel-CTD) for the patients with relapsed/refractory myeloma.

METHODS: Fifty-three patients who had received at least four cycles of treatment were enrolled. Bortezomib was given at 1.3 mg/m² on D1, 4, 8, 11, thalidomide 50 mg/day, daily, cyclophosphamide 150 mg/m² P.O. on D1–4, and dexamethasone 20 mg/m² I.V. or P.O. on D1, 4, 8, 11.

RESULTS: There were 26 males (49.1%) and 27 females (50.9%). The median age of patients was 67 years (range, 40–78 years). Median number of the previous treatment regimens was two (range, 1~5). Of total 53 patients, forty-nine patients (92.5%) achieved at least a partial response (PR) including 28 (52.8%) with complete response (CR) and 21 (42.9%) with PR as their best response. Median progression-free survival (PFS) was 14.7 months (range; 12.3–17.1 months) and median overall survival (OS), from the onset of vel-CTD was 31.6 months (range; 23.3–39.9 months). Patients who achieved a good response at least a PR after four cycles of vel-CTD showed longer PFS than those with poor therapeutic responses (2yr PFS, 28±8.7% vs. 0%, p=0.03). Further, patients who achieved a good therapeutic responses also showed significantly longer OS than those with poor responses (2yr OS, 72.3±8.3% vs. 33.3±15.7%, p=0.009). Grade 3–4 toxicities included thrombocytopenia (30.2%), neutropenia (11.3%), peripheral sensory neuropathy (32.1%), and thrombosis (3.8%). There was no treatment-related death.

CONCLUSIONS: Vel-CTD is a highly active salvage therapy in patients with relapsed/refractory myeloma. However, frequent side effects such as peripheral neuropathy should be considered. Furthermore, trials evaluating novel treatment approaches after bortezomib should be offered to reduce the rate of disease progression, particularly in patients who fail to show a good response at least PR after four cycles of therapy.