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Clinical Trial
. 2015 Nov;171(3):344-54.
doi: 10.1111/bjh.13582. Epub 2015 Jul 7.

Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up

Heinz Ludwig  1 , Richard Greil  2 , Tamas Masszi  3 , Ivan Spicka  4 , Ofer Shpilberg  5 , Roman Hajek  6 , Anna Dmoszynska  7 , Bruno Paiva  8 , María-Belén Vidriales  9 , Graca Esteves  10 , Anne Marie Stoppa  11 , Don Robinson Jr  12 , Shalini Chaturvedi  13 , Ozlem Ataman  14 , Christopher Enny  13 , Huaibao Feng  13 , Helgi van de Velde  15 , Luisa Viterbo  16
Affiliations
Clinical Trial

Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up

Heinz Ludwig et al. Br J Haematol. 2015 Nov.

Abstract

This follow-up extension of a randomised phase II study assessed differences in long-term outcomes between bortezomib-thalidomide-dexamethasone (VTD) and VTD-cyclophosphamide (VTDC) induction therapy in multiple myeloma. Newly diagnosed patients (n = 98) were randomised 1:1 to intravenous bortezomib (1·3 mg/m(2); days 1, 4, 8, 11), thalidomide (100 mg; days 1-21), and dexamethasone (40 mg; days 1-4, 9-12), with/without cyclophosphamide (400 mg/m(2); days 1, 8), for four 21-day cycles before stem-cell mobilisation/transplantation. After a median follow-up of 64·8 months, median time-to-next therapy was 51·8 and 47·9 months with VTD and VTDC, respectively. Type of subsequent therapy was similar in both arms. After adjusting for asymmetric censoring, median time to progression was not significantly different between VTD and VTDC [35·7 vs. 34·5 months; Hazard ratio (HR) 1·26, 95% confidence interval: 0·76-2·09; P = 0·370]. Five-year survival was 69·1% and 65·3% with VTD and VTDC, respectively. When analysed by minimal residual disease (MRD) status, overall survival was longer in MRD-negative versus MRD-positive patients with bone marrow-confirmed complete response (HR 3·66, P = 0·0318). VTD induction followed by transplantation provides long-term disease control and, consistent with the primary analysis, there is no additional benefit from adding cyclophosphamide. This study was registered at ClinicalTrials.gov (NCT00531453).

Keywords: minimal residual disease; multiple myeloma; transplantation.

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Figures

Figure 1
Figure 1
Time to progression (TTP) and progression‐free survival (PFS) with VTD and VTDC. (A) TTP per the primary analysis, with asymmetric censoring between arms. (B) TTP per the sensitivity analysis. (C) PFS per the primary analysis. (D) PFS per the sensitivity analysis. CI: confidence interval; HR: hazard ratio; NE: not estimatable; VTD, bortezomib‐thalidomide‐dexamethasone; VTDC, bortezomib‐thalidomide‐dexamethasone plus cyclophosphamide.
Figure 2
Figure 2
Time‐to‐next therapy (TTNT) and overall survival (OS) with VTD and VTDC. (A) TTNT. (B) OS. CI: confidence interval; HR: hazard ratio; NE: not estimatable; VTD, bortezomib‐thalidomide‐dexamethasone; VTDC, bortezomib‐thalidomide‐dexamethasone plus cyclophosphamide.
Figure 3
Figure 3
Overall survival (OS) according to minimal residual disease (MRD) status and response (pooled across VTD and VTDC arms). Kaplan–Meier analyses of OS in: (A) patients who achieved CR flc, ≥VGPR but excluding the CR flc patients, or <VGPR; (B) patients with bone marrow‐confirmed CR who were MRD‐negative or MRD‐positive; (C) MRD‐negative patients who achieved CR flc or other responses. CI: confidence interval; CR: complete response; CR flc: CR with normalized serum free light chain ratio; HR: hazard ratio; NE: not estimatable; VGPR: very good partial response; VTD, bortezomib‐thalidomide‐dexamethasone; VTDC, bortezomib‐thalidomide‐dexamethasone plus cyclophosphamide.
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References

    1. Anderson, K.C. , Alsina, M. , Bensinger, W. , Biermann, J.S. , Cohen, A.D. , Devine, S. , Djulbegovic, B. , Faber, E.A. Jr , Gasparetto, C. , Hernandez‐Illizaliturri, F. , Huff, C.A. , Kassim, A. , Krishnan, A.Y. , Liedtke, M. , Meredith, R. , Raje, N. , Schriber, J. , Singhal, S. , Somlo, G. , Stockerl‐Goldstein, K. , Treon, S.P. , Weber, D. , Yahalom, J. , Yunus, F. , Shead, D.A. & Kumar, R. (2013) Multiple myeloma, version 1.2013. Journal of the National Comprehensive Cancer Network, 11, 11–17. - PubMed
    1. Cavo, M. , Tacchetti, P. , Patriarca, F. , Petrucci, M.T. , Pantani, L. , Galli, M. , Di, R.F. , Crippa, C. , Zamagni, E. , Palumbo, A. , Offidani, M. , Corradini, P. , Narni, F. , Spadano, A. , Pescosta, N. , Deliliers, G.L. , Ledda, A. , Cellini, C. , Caravita, T. , Tosi, P. & Baccarani, M. (2010) Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem‐cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. The Lancet, 376, 2075–2085. - PubMed
    1. Cavo, M. , Pantani, L. , Petrucci, M.T. , Patriarca, F. , Zamagni, E. , Donnarumma, D. , Crippa, C. , Boccadoro, M. , Perrone, G. , Falcone, A. , Nozzoli, C. , Zambello, R. , Masini, L. , Furlan, A. , Brioli, A. , Derudas, D. , Ballanti, S. , Dessanti, M.L. , de Stefano, V. , Carella, A.M. , Marcatti, M. , Nozza, A. , Ferrara, F. , Callea, V. , Califano, C. , Pezzi, A. , Baraldi, A. , Grasso, M. , Musto, P. & Palumbo A. (2012) Bortezomib‐thalidomide‐dexamethasone is superior to thalidomide‐dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood, 120, 9–19. - PubMed
    1. Cavo, M. , Galli, M. , Pezzi, A. , di Raimondo, F. , Crippa, C. , Offidani, M. , Tacchetti, P. , Montefusco, V. , Narni, F. , Spadano, A. , Pescosta, N. , Zamagni, E. , Gamberi, B. , Caravita, T. , Falcone, A.P. , Nozzoli, C. , Zambello, R. , Furlan, A. , Brioli, A. & Boccadaro, M. (2013) Persistent improvement in clinical outcomes with bortezomib‐thalidomide‐dexamethasone vs thalidomide‐dexamethasone incorporated into double autologous transplantation for multiple myeloma: an updated analysis of phase 3 GIMEMA‐MMY‐3006 study. Blood, 122, 2090.
    1. Cavo, M. , Pantani, L. , Pezzi, A. , Cavallo, F. , Petrucci, M.T. , Di Raimondo, F. , Patriarca, F. , Waage, A. , Zamagni, E. , Montefusco, V. , Galli, M. , Gamberi, B. , Rossi, G. , Tacchetti, P. , Grasso, M. , Zweegman, S. , Offidani, M. , Ballanti, S. , Zambello, R. , Liberati, A.M. , Bassan, R. , Pregno, P. , Palumbo, A. & Sonneveld, P. (2014) Superior efficacy of VTD over VCD as induction therapy for autotransplantation‐eligible, newly diagnosed, myeloma patients. Blood, 124, 197.

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