TY - JOUR
T1 - Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma
AU - Ludwig, Heinz
AU - Viterbo, Luisa
AU - Greil, Richard
AU - Masszi, Tamas
AU - Spicka, Ivan
AU - Shpilberg, Ofer
AU - Hajek, Roman
AU - Dmoszynska, Anna
AU - Paiva, Bruno
AU - Vidriales, María Belén
AU - Esteves, Graca
AU - Stoppa, Anne Marie
AU - Robinson, Don
AU - Ricci, Deborah
AU - Cakana, Andrew
AU - Enny, Christopher
AU - Feng, Huaibao
AU - Van De Velde, Helgi
AU - Harousseau, Jean Luc
PY - 2013/1/10
Y1 - 2013/1/10
N2 - Purpose Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety. Patients and Methods Patients age 18 to 70 years with previously untreated, measurable MM, who were eligible for high-dose chemotherapy-autologous stem-cell transplantation (HDCT-ASCT), were randomly assigned to bortezomib 1.3 mg/m2, thalidomide 100 mg, and dexamethasone 40 mg, with (n = 49) or without (n = 49) cyclophosphamide 400 mg/m2 for four 21-day cycles, followed by HDCT-ASCT. The primary end point was postinduction combined rate of near-complete response (nCR) or better (including complete response [CR] with normalized serum κ CR, and nCR). Results Postinduction, 51% (VTD) and 44% (VTDC) of patients achieved combined CR/nCR, with bone marrow-confirmed CR in 29% and 31%, overall response rates of 100% and 96%, respectively, and very good partial response or better rates of 69% per arm. Post-HDCT-ASCT, combined CR/nCR rates were 85% (VTD) and 77% (VTDC). In all, 35% (VTD) and 27% (VTDC) of patients were negative for minimal residual disease (MRD) during induction and postinduction. Three-year overall survival was 80% (both arms). Grade 3 to 4 adverse events (AEs) and serious AEs were observed in 47% and 22% (VTD) and 57% and 41% (VTDC) of patients, respectively. The primary health-related quality of life end point (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] Global Health score) steadily increased with VTD during induction and reached a clinically relevant difference posttransplantation versus baseline. Conclusion Both VTD and VTDC are highly active induction regimens producing high combined CR/nCR and MRD-negative rates; however, VTDC was associated with increased toxicity and suggestion of transient decreases in Global Health score, without an increase in activity.
AB - Purpose Bortezomib-thalidomide-dexamethasone (VTD) is an effective induction therapy in multiple myeloma (MM). This phase II, noncomparative study sought to determine whether addition of cyclophosphamide to this regimen (VTDC) could further increase efficacy without compromising safety. Patients and Methods Patients age 18 to 70 years with previously untreated, measurable MM, who were eligible for high-dose chemotherapy-autologous stem-cell transplantation (HDCT-ASCT), were randomly assigned to bortezomib 1.3 mg/m2, thalidomide 100 mg, and dexamethasone 40 mg, with (n = 49) or without (n = 49) cyclophosphamide 400 mg/m2 for four 21-day cycles, followed by HDCT-ASCT. The primary end point was postinduction combined rate of near-complete response (nCR) or better (including complete response [CR] with normalized serum κ CR, and nCR). Results Postinduction, 51% (VTD) and 44% (VTDC) of patients achieved combined CR/nCR, with bone marrow-confirmed CR in 29% and 31%, overall response rates of 100% and 96%, respectively, and very good partial response or better rates of 69% per arm. Post-HDCT-ASCT, combined CR/nCR rates were 85% (VTD) and 77% (VTDC). In all, 35% (VTD) and 27% (VTDC) of patients were negative for minimal residual disease (MRD) during induction and postinduction. Three-year overall survival was 80% (both arms). Grade 3 to 4 adverse events (AEs) and serious AEs were observed in 47% and 22% (VTD) and 57% and 41% (VTDC) of patients, respectively. The primary health-related quality of life end point (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [EORTC QLQ-C30] Global Health score) steadily increased with VTD during induction and reached a clinically relevant difference posttransplantation versus baseline. Conclusion Both VTD and VTDC are highly active induction regimens producing high combined CR/nCR and MRD-negative rates; however, VTDC was associated with increased toxicity and suggestion of transient decreases in Global Health score, without an increase in activity.
UR - http://www.scopus.com/inward/record.url?scp=84872460585&partnerID=8YFLogxK
U2 - 10.1200/JCO.2011.39.5137
DO - 10.1200/JCO.2011.39.5137
M3 - Article
C2 - 23091109
AN - SCOPUS:84872460585
SN - 0732-183X
VL - 31
SP - 247
EP - 255
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 2
ER -