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

Heinz Ludwig, Richard Greil, T. Masszi, Ivan Spicka, Ofer Shpilberg, Roman Hajek, Anna Dmoszynska, Bruno Paiva, María Belén Vidriales, Graca Esteves, Anne Marie Stoppa, Don Robinson, Shalini Chaturvedi, Ozlem Ataman, Christopher Enny, Huaibao Feng, Helgi van de Velde, Luisa Viterbo

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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/m2; 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/m2; 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).

Original languageEnglish
Pages (from-to)344-354
Number of pages11
JournalBritish Journal of Haematology
Volume171
Issue number3
DOIs
Publication statusPublished - Nov 1 2015

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Thalidomide
Multiple Myeloma
Cyclophosphamide
Dexamethasone
Residual Neoplasm
Hematopoietic Stem Cell Mobilization
Survival
Stem Cell Transplantation
Bortezomib
Therapeutics
Transplantation
Bone Marrow
Confidence Intervals

Keywords

  • Minimal residual disease
  • Multiple myeloma
  • Transplantation

ASJC Scopus subject areas

  • Hematology

Cite this

Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma : 5-year follow-up. / Ludwig, Heinz; Greil, Richard; Masszi, T.; Spicka, Ivan; Shpilberg, Ofer; Hajek, Roman; Dmoszynska, Anna; Paiva, Bruno; Vidriales, María Belén; Esteves, Graca; Stoppa, Anne Marie; Robinson, Don; Chaturvedi, Shalini; Ataman, Ozlem; Enny, Christopher; Feng, Huaibao; van de Velde, Helgi; Viterbo, Luisa.

In: British Journal of Haematology, Vol. 171, No. 3, 01.11.2015, p. 344-354.

Research output: Contribution to journalArticle

Ludwig, H, Greil, R, Masszi, T, Spicka, I, Shpilberg, O, Hajek, R, Dmoszynska, A, Paiva, B, Vidriales, MB, Esteves, G, Stoppa, AM, Robinson, D, Chaturvedi, S, Ataman, O, Enny, C, Feng, H, van de Velde, H & Viterbo, L 2015, 'Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up', British Journal of Haematology, vol. 171, no. 3, pp. 344-354. https://doi.org/10.1111/bjh.13582
Ludwig, Heinz ; Greil, Richard ; Masszi, T. ; Spicka, Ivan ; Shpilberg, Ofer ; Hajek, Roman ; Dmoszynska, Anna ; Paiva, Bruno ; Vidriales, María Belén ; Esteves, Graca ; Stoppa, Anne Marie ; Robinson, Don ; Chaturvedi, Shalini ; Ataman, Ozlem ; Enny, Christopher ; Feng, Huaibao ; van de Velde, Helgi ; Viterbo, Luisa. / Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma : 5-year follow-up. In: British Journal of Haematology. 2015 ; Vol. 171, No. 3. pp. 344-354.
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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/m2; 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/m2; 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).",
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