Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial

Abstract

We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis. No clinically relevant differences in ORR post-induction were seen between patients with or without high-risk cytogenetic abnormalities (86·2% vs. 84·3%). Further follow-up data are available for 113 patients receiving ASCT who were included in a prospective consolidation trial (median follow-up, 55·5 months); median progression-free survival (PFS) was 35·3 months and median overall survival (OS) was not reached. In patients with high-risk versus standard-risk cytogenetics, median PFS was 19·9 vs. 43·6 months (P < 0·0001), and median OS was 54·7 months versus not reached (P = 0·0022). VCD is an effective and tolerable induction regimen; results suggest that VCD induces high response rates independently of cytogenetic risk status, but after long-term follow-up, cytogenetic high risk is associated with markedly reduced PFS and OS post-ASCT.

Stem cell transplant and the potential role of CAR-T cells in multiple myeloma

“…Aft er a median follow-up of 68.7 months, they reported good 8-year PFS (43%) and OS (67%) following allogeneic transplant in 61 patients who received escalating DLI. Low GVHD incidence was also observed (33%) with no DLI related mortality [34] in the same reference. On the other hand, Edwin et al did not observe a diff erence in the incidence of GVHD when the patients received DLI at less than one year versus > 1 year aft er BMT, as shown by Alyea et al [40,42].…”

Proteasome Inhibitors for the Treatment of Multiple Myeloma

“…VCD has demonstrated a high response rate in prospective phase II and phase III clinical trials [24,[39][40][41]. The IFM conducted a randomized trial of head-to-head comparison between VTD and VCD prior to ASCT in patients with untreated MM [27].…”

Structured assessment of frailty in multiple myeloma as a paradigm of individualized treatment algorithms in cancer patients at advanced age

“…These include bortezomibcyclophosphamide-dexamethasone (VCD), bortezomiblenalidomide-dexamethasone (VRD or VTD), bortezomibmelphalan-prednisone (VMP) or antibody-combinations, autologous stem cell transplantation (ASCT) and 2-drug combinations, such as lenalidomide-dexamethasone (Rd), bortezomib-dexamethasone (Vd), and others. 3,[20][21][22] These largely expanded therapeutic strategies, including immunotherapies, 23 have significantly evolved in recent years, but the beneficial effect is not seen across the age spectrum, with intermediate-fit or frail patients not obtaining the maximal benefit from such new treatment. Part of this failure to achieve benefit relates to the host biology of older patients.…”