Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial
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Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial. / Sonneveld, Pieter; Schmidt-Wolf, Ingo G H; van der Holt, Bronno; El Jarari, Laila; Bertsch, Uta; Salwender, Hans; Zweegman, Sonja; Vellenga, Edo; Broyl, Annemiek; Blau, Igor W; Weisel, Katja C; Wittebol, Shulamiet; Bos, Gerard M J; Stevens-Kroef, Marian; Scheid, Christof; Pfreundschuh, Michael; Hose, Dirk; Jauch, Anna; van der Velde, Helgi; Raymakers, Reinier; Schaafsma, Martijn R; Kersten, Marie-Jose; van Marwijk-Kooy, Marinus; Duehrsen, Ulrich; Lindemann, Walter; Wijermans, Pierre W; Lokhorst, Henk M; Goldschmidt, Hartmut M.
in: J CLIN ONCOL, Jahrgang 30, Nr. 24, 20.08.2012, S. 2946-55.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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.
KW - Adult
KW - Aged
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Boronic Acids
KW - Bortezomib
KW - Dexamethasone
KW - Disease-Free Survival
KW - Doxorubicin
KW - Drug Administration Schedule
KW - Female
KW - Humans
KW - Maintenance Chemotherapy
KW - Male
KW - Middle Aged
KW - Multiple Myeloma
KW - Pyrazines
KW - Remission Induction
KW - Thalidomide
KW - Vincristine
KW - Clinical Trial, Phase III
KW - Journal Article
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1200/JCO.2011.39.6820
DO - 10.1200/JCO.2011.39.6820
M3 - SCORING: Journal article
C2 - 22802322
VL - 30
SP - 2946
EP - 2955
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 24
ER -
