Bortezomib plus dexamethasone can improve stem cell collection and overcome the need for additional chemotherapy before autologous transplant in patients with myeloma

Abstract

The aim of this phase II trial was to investigate the efficacy of bortezomib plus dexamethasone (Vel-Dex) as induction therapy in patients with multiple myeloma (MM) and to define the role of intensification before transplantation. Fifty-seven patients were treated with four courses of Vel-Dex, two cycles of dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP), and a single autologous transplant. Fourteen patients (25%) went off-study: seven after Vel-Dex, seven after DCEP. All patients yielded high numbers of stem cells (median CD34+ cells 7.5 x 106/kg); 54 of the 57 patients (94%) collected > or =4 x 106/kg CD34+ cells, 60% with a single leukapheresis. The overall response rate (ORR) after Vel-Dex was 86% (70% had a very good partial response [VGPR] or better) regardless of cytogenetic abnormalities and International Staging System stage (ISS). The response at the end of the two DCEP cycles remained unchanged in 35 patients (70%), worsened in 15 (20%), and improved in 5 (10%). Because of the consistent drop-out, the ORR in intention-to-treat analysis decreased significantly from 86% after Vel-Dex to 76% after DCEP, and 73% after transplantation. However, when considering the subset of 43 patients who completed the program, the ORR was 96% (complete response 39%, VGPR 41%, partial response 16%). In conclusion, Vel-Dex produces high response rates, improves stem cell collection, and overcomes the need for intensification before autologous transplantation.

Proteasome inhibitors in multiple myeloma: 10 years later

“…Several phase 2 trials investigated bortezomib-dexamethasone induction, with response rates of 66% to 90%, including 15% to 21% CR and 31% to 70% very good PR (VGPR) or better. [63][64][65] This translated into high CR and VGPR rates after transplantation. Toxicities were generally mild to moderate and proved manageable, without treatmentrelated mortality, and stem cell collection was adequate.…”

Phase II study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma

“…The regimen is active as induction therapy prior to autologous stem cell transplantation in the frontline setting. [1][2][3][4] Bortezomib alone or in combination with dexamethasone has also demonstrated activity in multiple studies in the relapsed setting. [5][6][7][8][9][10][11][12][13] However, no studies have prospectively assessed bortezomib-dexamethasone (from cycle 1) as second-line therapy in MM, although one phase II study has investigated the addition of dexamethasone for sub-optimal response to single-agent bortezomib in patients at first relapse or refractory to front-line therapy, demonstrating improved responses with the addition of dexamethasone.…”

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma

“…Additionally, 80% of patient required a single apheresis session to achieve a sufficient collection. Bortezomib based therapy has shown to lead to robust CD34+ stem cell yields during collection . Our results suggest an enhancing effect of carfilzomib on stem cell mobilization as well, thus establishing Kd induction as an acceptable regimen for transplant‐eligible patient induction.…”