VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial

Abstract

Key Points• The overall response rate following 4 induction cycles of VTD prior to ASCT is higher than that of 4 cycles of VCD.The Intergroupe Francophone du Myélome conducted a randomized trial to compare bortezomib-thalidomide-dexamethasone (VTD) with bortezomib-cyclophosphamidedexamethasone (VCD) as induction before high-dose therapy and autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma. Overall, a total of 340 patients were centrally randomly assigned to receive VTD or VCD. After 4 cycles, on an intent-to-treat basis, 66.3% of the patients in the VTD arm achieved at least a very good partial response (primary end point) vs 56.2% in the VCD arm (P 5 .05). In addition, the overall response rate was significantly higher in the VTD arm (92.3% vs 83.4% in the VCD arm; P 5 .01). Hematologic toxicity was higher in the VCD arm, with significantly increased rates of grade 3 and 4 anemia, thrombocytopenia, and neutropenia. On the other hand, the rate of peripheral neuropathy (PN) was significantly higher in the VTD arm. With the exception of hematologic adverse events and PN, other grade 3 or 4 toxicities were rare, with no significant differences between the VTD and VCD arms. Our data support the preferential use of VTD rather than VCD in preparation for ASCT.

Efficacy and Safety of a Weekly Cyclophosphamide-Bortezomib-Dexamethasone Regimen as Induction Therapy Prior to Autologous Stem Cell Transplantation in Japanese Patients with Newly Diagnosed Multiple Myeloma: A Phase 2 Multicenter Trial

“…When considering the therapeutic power of CBD as induction therapy, a phase 3 study by Moreau et al [15] that compared the efficacy of CBD with bortezomib-thalidomide-dexamethasone should be discussed [15]. They demonstrated the superior efficacy of bortezomib-thalidomide-dexamethasone over CBD, which was also confirmed earlier by a meta-analysis [17].…”

“…Although several studies have evaluated the efficacy of CBD induction regimens in phase 2 or 3 settings, the response rates observed in those previous studies vary [6, 7, 12-15] (Table 4). One critical issue for interpreting the results of these previous CBD trials is the variable schedule and the dose of induction chemotherapy.…”

How I manage the toxicities of myeloma drugs

“…21 Cyclophosphamide, 22,23 or the IMiDs thalidomide 23,24 and lenalidomide, 25 is the typical partner drug in the bortezomib-dexamethasone backbone. Switching from intravenous to subcutaneous 5 and from twice-to once-weekly administration 26 has significantly reduced the incidence and severity of BiPN compared with the pivotal studies 3,4 ; still, up to one-third of patients develop clinically significant peripheral neuropathy (PN) during bortezomib treatment (Table 1).…”

How I treat myeloma with new agents

“…7,9 Based on response rates, depth of response, and PFS as surrogate markers for outcome, 3-drug combinations, including bortezomib and dexamethasone, are currently the standard of care as induction therapy prior to ASCT, but only limited data from prospective phase III trials are available to demonstrate that one combination is superior to the other. 1,4,10,11 Four to six courses of induction are recommended before proceeding to stem cell collection. 1 The preferred regimens consist of VCD, RVD, or bortezomib-dexamethasone plus thalidomide or doxorubicin.…”