Conference Correspondent

Bortezomib/Thalidomide/Dexamethasone (VTD) Is Superior to Bortezomib/Cyclophosphamide/ Dexamethasone (VCD) Prior to ASCT for Patients with De Novo MM

Conference Correspondent 

Triplet combinations of bortezomib/thalidomide/dexamethasone (VTD) and bortezomib/cyclophosphamide/dexamethasone (VCD) are 2 of the most commonly used induction regimens prior to autologous stem-cell transplant (ASCT), and are both recommended in the National Comprehensive Cancer Network guidelines for the treatment of de novo multiple myeloma (MM). However, no comparative data from prospective randomized trials of the safety and efficacy of VTD versus VCD have been published to date.

In this study, patients with newly diagnosed symptomatic MM less than 66 years of age were prospectively randomized to receive either 4 cycles of VTD or 4 cycles of VCD followed by ASCT. The VTD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m²/day, administered subcutaneously on days 1, 4, 8, and 11; dexamethasone 40 mg/day, administered orally on days 1 to 4 and 9 to 12; and thalidomide 100 mg/day, administered orally on days 1 to 21. The VCD regimen consisted of four 21-day cycles of bortezomib 1.3 mg/m2/day, administered subcutaneously on days 1, 4, 8, and 11; dexamethasone 40 mg/day, administered orally on days 1 to 4 and 9 to 12; and cyclophosphamide 500 mg/m2/day, administered orally on days 1, 8, and 15. Patients were stratified according to the International Staging System (1-2 vs 3) and cytogenetics (high risk defined by 17p deletion and t[4;14] vs other). The primary end point was very good partial response (VGPR) rate following 4 cycles.

A total of 358 patients enrolled in the study, 18 of which did not meet the inclusion criteria. The remaining patients were randomized; 170 each to the VTD and VCD arms. One patient in each arm withdrew consent or was deemed ineligible, leaving 169 evaluable patients in each arm. The median age was 60 years, and 62% of the patients were male.

In the per-protocol analysis, the overall response rate, as measured by partial response or better, was 98.7% in the VTD arm, including a 14.0% complete response (CR) rate and a VGPR rate of 70.7%.  In the VCD arm, the overall response rate was 90.3%, with a 9.1% CR and a 60.42% VGPR rate. VGPR and partial response (PR) rates were significantly higher in the VTD arm with P values of .05 and .0001, respectively. In terms of adverse events, grade 3/4 peripheral neuropathy occurred in 7.7% of patients in the VTD arm versus 2.9% of patients in the VCD arm, and grade 3/4 neutropenia was seen in 18.9% of patients in the VTD arm versus 33.1% in the VCD arm.

In this prospective randomized controlled trial, the data demonstrate that VTD is significantly superior to VCD in terms of VGPR and PR rates, underscoring the synergistic activity of immunomodulatory drugs and proteasome inhibitors. Overall, both regimens were relatively well tolerated; however, neutropenia occurred more frequently in patients receiving VCD.

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