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.
RCT Entities:
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.
Authors: Christof Scheid; Pieter Sonneveld; Ingo G H Schmidt-Wolf; Bronno van der Holt; Laila el Jarari; Uta Bertsch; Hans Salwender; Sonja Zweegman; Igor Wolfgang Blau; Edo Vellenga; Katja Weisel; Michael Pfreundschuh; Kon-Siong Jie; Kai Neben; Helgi van de Velde; Ulrich Duehrsen; M Ron Schaafsma; Walter Lindemann; Marie José Kersten; Norma Peter; Mathias Hänel; Sandra Croockewit; Hans Martin; Shulamiet Wittebol; Gerard Mj Bos; Marinus van Marwijk-Kooy; Pierre Wijermans; Hartmut Goldschmidt; Henk M Lokhorst Journal: Haematologica Date: 2013-08-30 Impact factor: 9.941
Authors: Siyang Leng; Suzanne Lentzsch; Yanhan Shen; Wei-Yann Tsai; Jason Dennis Wright; Dawn Lauryn Hershman; Alfred I Neugut Journal: Leuk Lymphoma Date: 2018-02-02
Authors: Christian Straka; Peter Liebisch; Hans Salwender; Burkhard Hennemann; Bernd Metzner; Stefan Knop; Sigrid Adler-Reichel; Christian Gerecke; Hannes Wandt; Martin Bentz; Tim Hendrik Bruemmendorf; Marcus Hentrich; Michael Pfreundschuh; Hans-Heinrich Wolf; Orhan Sezer; Ralf Bargou; Wolfram Jung; Lorenz Trümper; Bernd Hertenstein; Else Heidemann; Helga Bernhard; Nicola Lang; Norbert Frickhofen; Holger Hebart; Ralf Schmidmaier; Andreas Sandermann; Tobias Dechow; Albrecht Reichle; Brigitte Schnabel; Kerstin Schäfer-Eckart; Christian Langer; Martin Gramatzki; Axel Hinke; Bertold Emmerich; Hermann Einsele Journal: Haematologica Date: 2016-08-04 Impact factor: 9.941