Clinical Efficacy of a Bortezomib, Cyclophosphamide and Dexamethasone Compared with Bortezomib, Cyclophosphamide, Thalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma

Salvage therapy such as bortezomib, cyclophosphamide, thalidomide and dexamethasone (Vel-CTD) showed an effective regimen in patients with relapsed or refractory multiple myeloma (MM). However, toxicities of this regimen due to combination bortezomib and thalidomide interrupt the consecutive treatments in a few patients. Therefore, we compared the clinical responses and toxicities between bortezomib, cyclophosphamide and dexamethasone (Vel-CD) and Vel-CTD in patients with relapsed or refractory MM patients, retrospectively.

Eighty-six patients received at least 2 cycles of treatment with Vel-CTD (bortezomib 1.3 mg/m² i.v. on D1, 4, 8 and 11; cyclophosphamide 150 mg/m² orally on D1-4; thalidomide 50 mg/day orally every day; and dexamethasone 20 mg/m² i.v. on D1, 4, 8 and 11 for every 3 weeks) and 67 patients with Vel-CD, which is the same regimen except thalidomide. Vel-CD group was only received low-dose acyclovir for prevention of herpes zoster.

17/67 (25%) and 10/86 (12%) of light chain disease was enrolled in Vel-CD and Vel-CTD group respectively (p=0.027) and there was no statistical difference at baseline demographic and disease characteristics between two groups in the others. The median time from diagnosis to treatment in Vel-CD and Vel-CTD was 15.6 months (range, 2–250 months) and 15.7 months (range, 1–230 months), respectively (p=0.54). The median number of treatment cycles was 6 cycles (range, 2–18) in Vel-CD and 8 cycles (range, 2–24) in Vel CTD group, and the number of cycles delivered was 430 and 678, respectively. The overall response rates (≥PR) of Vel-CD and Vel-CTD group were 88% and 90% ( 49% and 48% of complete response, 9% and 14% of very good partial response, 30% and 28% of partial response), respectively (each, p>0.05). There was no difference in progression free survival (p=0.69) and overall survival (p=0.49). Grade 3 or more hematologic adverse events occurred in the same proportion of patients in the both group. In non hematologic toxicities profiles, Vel-CTD group (14%) showed the higher proportion of grade 3 or more sensory neuropathy compared with Vel-CD group (3%) (p=0.02). Dose adjustment of bortezomib in Vel-CD and Vel-CTD were 40% (27/67) and 41%(35/86), respectively (p=0.96). Two patients (3%) in Vel-CD group received acyclovir prophylaxis developed herpes zoster compared with 17 patients (20%) in Vel-CTD group they were not received acyclovir prophylaxis (p=0.002). Three patients showed thrombotic events (2: pulmonary thromboembolism, 1: acute myocardial infarction) in only Vel-CTD group despite aspirin prophylaxis (p=0.16).

Vel-CD combination therapy in patients with relapsed or refractory MM is an effective and more tolerable salvage regimen compared with Vel-CTD in the aspect of comparable response rate, less non-hematologic toxicities especially thalidomide associated adverse events.

No relevant conflicts of interest to declare.