Short-course pretransplant velcade, thalidomide and dexamethasone regimen induces high complete response rate without compromising CD34+ cell collection in untreated multiple myeloma patients: preliminary results of a single-centre experience

Background: High-dose chemotherapy with autologous stem-cell support has significantly improved progression-free and overall survival of patients with untreated multiple myeloma (MM). Pre-transplant complete response (CR) and tumor reduction have been identified as most relevant prognostic factors for long-term survival in untreated MM. Recently, thalidomide and bortezomib both given as single agent shown to be effective in previously treated MM. Since they have target different molecular pathways their combination is waited to be highly effective to induce high CR rate and tumor reduction before HDT with stem-cell support. We present early data of this regimen in untreated symptomatic MM patients. Patients and Methods: From March 2007 to October 2008 16 pts (M/F: 12/4) were enrolled in the study; median age was 57 years (range: 42-71), 47% were older 60 years; Most of pts had stage III according to Durie & Salmon (76%) and ISS score 2-3(76%). M-component was IgG 69% (11/16), IgA 19%, and non secretory 12%. Regimen: Bortezomib was given at 1.3 mg/[m.sup.2] on days 1,4, 8, 11, thalidomide at dose of 100 mg PO daily, and dexamethasone (40 mg/die PO) was given the day of bortezomib and the day after (320 mg td for each cycle). All patients received 3 cycles of WTD every 4 weeks before CD34+ cell collection and high-dose melphalan (200 mg/[m.sup.2]). Deep-venous thrombosis prophylaxis was established in all pts consisting of aspirin 100 mg daily in 44% of pts, low-molecular weight heparin (28%) or low dose warfarin (28%). Results: all pts are evaluable for response to Velcade, Thalidomide and Dexamethasone (VTD) regimen and PBSC collection; 13 pts have been transplanted. After three VTD 88% of pts achieved PR including 47% of CR. VTD regimen was well tolerated with main toxicity consisting of WHO grade III peripheral neuropathy in 12% of pts. There was no chemotherapy reduction or delay due to toxicity. A median of 6.5 x 106/kg of CD34+ cells (range: 2.7-11.6) was collected in 15 of 16 pts. The median CD 34+ cells infused was 3.2 x [10.sup.6]/kg (range: 2.0-4.3). Times to platelet (20 x [10.sup.9]/L) and granulocyte (500x109/L) recovery were 13 and 10 days respectively. After VTD and transplant 10 of 13 patients achieved CR (75%) and 2 (15%) a VGPR. Conclusion: These very preliminary data suggest that VTD is effective and well tolerated regimen; high response rate without compromising PBSC collection makes it a good option for initial treatment of MM although