A comparison of lenalidomide/dexamethasone versus cyclophosphamide/lenalidomide/dexamethasone versus cyclophosphamide/bortezomib/dexamethasone in newly diagnosed multiple myeloma

Abstract

Summary Novel agents are considered standard components of induction therapy for newly diagnosed patients with multiple myeloma. We retrospectively compared the results of three consecutive phase 2 clinical trials; RD (lenalidomide/dexamethasone, n = 34), CRD (cyclophosphamide/lenalidomide/dexamethasone, n = 53) and CyBorD (cyclophosphamide/bortezomib/dexamethasone, n = 63) (N = 150). Response rates after four cycles of treatment were: ≥near complete response (nCR), 12% vs. 2% vs. 41%, P < 0·0001 and very good partial response or better, 35% vs. 30% vs. 65%, P = 0·0003, respectively. With all cycles of therapy considered, ≥nCR was 35%, 15% and 41%, P = 0·006. However, there is no evidence that one regimen produced superior progression‐free survival (PFS) (median: 3·2 vs. 2·3 vs. 2·7 years, P = 0·11) or overall survival (3‐year: 88% vs. 79% vs. 88%, P = 0·23). Transplantation did not impact PFS (median: 2·7 vs. 2·3 years, P = 0·41) but was associated with improved OS (3‐year: 93% vs. 75%, P ≤ 0·001). High genetic risk patients (n = 40) had earlier relapse despite lenalidomide or bortezomib (median: 2·1 vs. 2·7 years, P = 0·45). Grade 3/4 toxicities were least with CyBorD while CRD had most toxicity. In conclusion, CyBorD demonstrated superior responses and less frequent serious toxicity but more neuropathy when compared to RD and CRD. Importantly, 80% of patients treated with modern therapeutic approaches are alive at 4 years.

Long‐term survival with cyclophosphamide, bortezomib and dexamethasone induction therapy in patients with newly diagnosed multiple myeloma

“…Another common induction combination is lenalidomide and dexamethasone (RD). A comparison of RD, CyBorD and CRD showed similar survival at 3 years, but there are no prospective randomized trials comparing these regimens (Khan et al, 2012). In a recent analysis of patients treated with RD, the 5-year survival was 71%, similar to our patients teated with CyBorD (Srivastava et al, 2013).…”

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

“…These differences were not the result of dose attenuation or the use of a "VCD-light" regimen, as the dose of cyclophosphamide that was administered in our trial was 500 mg/m 2 on days 1, 8, and 15, which is higher than that reported in the retrospective study by Cavo et al (500 mg/ 2 on days 1 and 8) 16 or in other VCD regimens reported previously. [6][7][8] The dose intensity in both arms was high and was greater than 90% for each drug. The VGPR rate of 56% with VCD described in our trial (ITT) is much higher than the 37% VGPR rate reported by Mai et al in the prospective German trial 12 and the 37% VGPR rate that was reported by Cavo et al in the retrospective Italian analysis.…”

“…4 Based on response rates, depth of response, and PFS as surrogate markers for outcome, 3-drug combinations including bortezomib and dexamethasone plus either an immunomodulatory drug (IMiD) (thalidomide or lenalidomide), cyclophosphamide, or doxorubicin (PAD) are currently the standard of care prior to ASCT. [1][2][3][4][5] The triplet combinations bortezomibthalidomide-dexamethasone (VTD) and bortezomib-cyclophosphamidedexamethasone (VCD) have demonstrated high response rates in prospective phase 2 [6][7][8] and phase 3 [9][10][11][12] clinical trials, they are two of the most commonly used induction regimens prior to ASCT and are both recommended in the international guidelines. [1][2][3] To date, no comparative data from prospective randomized trials of the safety and efficacy of VTD vs VCD are available.…”

Long-term Follow-up of MRC Myeloma IX Trial: Survival Outcomes with Bisphosphonate and Thalidomide Treatment

“…Since this study was designed, data on new triple-combination induction therapies and novel emerging treatments have been published. For example, at least four new bortezomib-based triple combinations: bortezomib-thalidomide-dexamethasone (VTD), bortezomib-lenalidomide-dexamethasone (RVD), bortezomibdoxorubicin-dexamethasone (PAD), and cyclophosphamide-bortezomib-dexamethasone (CyBorD) have been described previously (25)(26)(27)(28)(29)(30). In terms of novel emerging treatments, phase I/II trials have investigated inductionmaintenance regimens including the two new proteasome inhibitors carfilzomib (carfilzomib-lenalidomide-dexamethasone induction with lenalidomide maintenance, and carfilzomib-cyclophosphamide-dexamethasone with carfilzomib maintenance) and ixazomib (ixazomib-lenalidomide-dexamethasone induction with ixazomib maintenance), and the histone deacetylase inhibitor vorinostat (RVD-vorinostat with lenalidomide AE bortezomib maintenance; refs.…”