The Combination of Cyclophosphamide, Velcade and Dexamethasone (CVD) Induces High Response Rates with Minimal Toxicity Compared to Velcade Alone (V) and Velcade Plus Dexamethasone (VD).

Bortezomib (Velcade®), as the first-in-class proteasome inhibitor, has shown to be effective for the treatment of relapsed refractory myeloma. Preclinical and/or clinical studies showed improved activity by combining this agent with a number of conventional chemotherapeutic agents, suggesting synergistic effects. We conducted a retrospective study to assess the efficacy and toxicity profile with Velcade alone and in combination with dexamethasone or cyclophosphamide, and dexamethasone for patients with multiply relapsed myeloma. 11 patients were treated with Velcade alone, 20 with the combination of Velcade and dexamethasone (VD), and 11 with the regimen comprising Velcade, dexamethasone and cyclophosphamide (CVD). Velcade 1.3mg/m² was given as a single bolus IV on days 1, 4, 8 and 11, dexamethasone 40mg po on the day of Velcade injection and the day thereafter, and cyclophosphamide 500 mg po days 1, 8, 15 of a 21 day cycle for a maximum of 9 cycles of treatment. No patient received prophylactic anticoagulation. Toxicity profiles and response were assessed every 3 weeks. There was no statistical difference of baseline characteristics (age, ISS, number of previous lines of treatment) among the three treatment groups (P>0.05). The overall response rates (CR+PR) within the three groups are 30% (V), 47% (VD), and 64% (CVD) respectively. The CR rate of CVD group is impressive at 27% compared to 5% with VD and 0% with V. The median duration of treatment of three groups (V vs VD vs CVD) are 115 days, 98 days and 116 days respectively (P>0.05). Thrombocytopenia and new/worsening peripheral neuropathy are the most common side effects in each group. Although thrombocytopenia and neutropenia occurred in the CVD group (36% and 27% respectively), it was at a similar frequency as in the groups of VD (50% and 15%) and V (64% and 45%). Grade 3 infection rates were also similar at 18%, 30% and 18% (V vs VD vs CVD). Peripheral neuropathy is the most troublesome side effect, and is the main reason for Velcade dose reduction and/or discontinuation in each group (27% V, 45% VD, 54% CVD). 27% of patients within CVD group required dose reduction of cyclophosphamide due to neutropenia. Median follow up is currently too limited to comment on whether the improved CR rate with CVD translates into an improved progression free survival. In conclusion CVD is a well tolerated regimen producing high overall and complete response rates, with no increase in toxicity compared to VD or V alone, and lacks the toxicity associated with Velcade- melphalan combinations.