High Response and Complete Remission Rates in Relapsed/Refractory Multiple Myeloma Treated with Bortezomib, Thalidomide, Dexamethasone and Zoledronic Acid (VTD-Z) Combination Therapy.

Purpose: Bortezomib (VELCADETM) is a novel proteasome inhibitor that has shown tremendous clinical efficacy either as a single agent or in combination with other cytotoxic agents in relapsed/refractory multiple myeloma (MM). In this study, we combined bortezomib (V) with thalidomide (Thal), dexamethasone (Dex) and zoledronic acid (Zol) to determine the efficacy and toxicity of this regimen (VTD-Z) in patients with relapsed/refractory MM.

Methods: Patients were treated for 2 to 11 three-weekly cycles of VTD-Z comprising: V 1.3 mg/m2 on days 1, 4, 8 and 11; Thal 50 mg ON; Dex 20 mg OM on days 1 to 4, 8 to 11, 15 to 18; and Zol 4 mg on day 1. Patients did not receive any prophylaxis for venous thrombosis. Response was graded according to Bladès criteria.

Results: Twelve patients (2 males, 10 females; median age 63.3 years) with relapsed/refractory MM were studied. Complex karyotypes were present in all (10 out of 10) patients who had karyotype studies performed at the time of diagnosis. Four patients had deletion chromosome 13 (del(13)). The overall response rate (RR) was 91.7% (11 out of 12), of which 50.0% (6) achieved complete remission (CR), 25.0% (3) achieved near-CRs (nCR), 16.7% (3) were partial responders (PR). There were no minimal responders (MR) and 1 (8.3%) non-responder (NR). Two patients who achieved CR had del(13). Transient grade 3 thrombocytopenia was the only severe adverse event and this was observed in 4 (33.3%) patients. Grade 2 peripheral neuropathy was observed in 4 (25.0%) of patients. None of the patients developed deep vein thrombosis or pulmonary embolism. The single NR was the only death that occurred during the period of study.

Conclusions: Our study demonstrates that the VTD-Z regimen is exceptionally effective and safe in patients with relapsed/refractory MM. The high CR/near-CR rates (total of 75.0%), attained after relatively few cycles of VTD-Z, suggest that these three drugs could be at least additive, if not, even synergistic. Longer term follow-up will be required to determine the durability of these responses.