TY - JOUR
T1 - Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/GMMG-HD4 Trial
AU - Sonneveld, Pieter
AU - Schmidt-Wolf, Ingo G. H.
AU - van der Holt, Bronno
AU - el Jarari, Laila
AU - Bertsch, Uta
AU - Salwender, Hans
AU - Zweegman, Sonja
AU - Vellenga, Edo
AU - Broyl, Annemiek
AU - Blau, Igor W.
AU - Weisel, Katja C.
AU - Wittebol, Shulamiet
AU - Bos, Gerard M. J.
AU - Stevens-Kroef, Marian
AU - Scheid, Christof
AU - Pfreundschuh, Michael
AU - Hose, Dirk
AU - Jauch, Anna
AU - van der Velde, Helgi
AU - Raymakers, Reinier
AU - Schaafsma, Martijn R.
AU - Kersten, Marie-Jose
AU - van Marwijk-Kooy, Marinus
AU - Duehrsen, Ulrich
AU - Lindemann, Walter
AU - Wijermans, Pierre W.
AU - Lokhorst, Henk M.
AU - Goldschmidt, Hartmut M.
PY - 2012/8/20
Y1 - 2012/8/20
N2 - Purpose We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). Patients and Methods In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage. Results Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P <.001) and bortezomib maintenance (34% v 49%; P <.001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [ HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P <.001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003). Conclusion Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.
AB - Purpose We investigated whether bortezomib during induction and maintenance improves survival in newly diagnosed multiple myeloma (MM). Patients and Methods In all, 827 eligible patients with newly diagnosed symptomatic MM were randomly assigned to receive induction therapy with vincristine, doxorubicin, and dexamethasone (VAD) or bortezomib, doxorubicin, and dexamethasone (PAD) followed by high-dose melphalan and autologous stem-cell transplantation. Maintenance consisted of thalidomide 50 mg (VAD) once per day or bortezomib 1.3 mg/m(2) (PAD) once every 2 weeks for 2 years. The primary analysis was progression-free survival (PFS) adjusted for International Staging System (ISS) stage. Results Complete response (CR), including near CR, was superior after PAD induction (15% v 31%; P <.001) and bortezomib maintenance (34% v 49%; P <.001). After a median follow-up of 41 months, PFS was superior in the PAD arm (median of 28 months v 35 months; hazard ratio [ HR], 0.75; 95% CI, 0.62 to 0.90; P = .002). In multivariate analysis, overall survival (OS) was better in the PAD arm (HR, 0.77; 95% CI, 0.60 to 1.00; P = .049). In high-risk patients presenting with increased creatinine more than 2 mg/dL, bortezomib significantly improved PFS from a median of 13 months to 30 months (HR, 0.45; 95% CI, 0.26 to 0.78; P = .004) and OS from a median of 21 months to 54 months (HR, 0.33; 95% CI, 0.16 to 0.65; P <.001). A benefit was also observed in patients with deletion 17p13 (median PFS, 12 v 22 months; HR, 0.47; 95% CI, 0.26 to 0.86; P = .01; median OS, 24 months v not reached at 54 months; HR, 0.36; 95% CI, 0.18 to 0.74; P = .003). Conclusion Bortezomib during induction and maintenance improves CR and achieves superior PFS and OS.
U2 - 10.1200/JCO.2011.39.6820
DO - 10.1200/JCO.2011.39.6820
M3 - Article
C2 - 22802322
SN - 0732-183X
VL - 30
SP - 2946
EP - 2955
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 24
ER -