Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma

FIRST Trial Team

Research output: Contribution to journalArticle

401 Citations (Scopus)

Abstract

Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. Conclusions: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.

Original languageEnglish (US)
Pages (from-to)906-917
Number of pages12
JournalNew England Journal of Medicine
Volume371
Issue number10
DOIs
StatePublished - Sep 4 2014

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Dexamethasone
Melphalan
Thalidomide
Prednisone
Transplants
Disease-Free Survival
Stem Cell Transplantation
lenalidomide
Survival
Disease Progression
Second Primary Neoplasms
Poisons
Multiple Myeloma
Nervous System
Odds Ratio

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. / FIRST Trial Team.

In: New England Journal of Medicine, Vol. 371, No. 10, 04.09.2014, p. 906-917.

Research output: Contribution to journalArticle

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title = "Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma",
abstract = "Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59{\%} with continuous lenalidomide-dexamethasone, 56{\%} with 18 cycles of lenalidomide-dexamethasone, and 51{\%} with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70{\%} vs. 78{\%}). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. Conclusions: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.",
author = "{FIRST Trial Team} and Lotfi Benboubker and Dimopoulos, {Meletios A.} and Angela Dispenzieri and John Catalano and Belch, {Andrew R.} and Michele Cavo and Antonello Pinto and Katja Weisel and Heinz Ludwig and Nizar Bahlis and Anne Banos and Mourad Tiab and Michel Delforge and Jamie Cavenagh and Catarina Geraldes and Lee, {Je Jung} and Christine Chen and Albert Oriol and {De La Rubia}, Javier and Lugui Qiu and White, {Darrell J.} and Daniel Binder and Kenneth Anderson and Fermand, {Jean Paul} and Philippe Moreau and Michel Attal and Robert Knight and Guang Chen and {Van Oostendorp}, Jason and Christian Jacques and Annette Ervin-Haynes and Herv{\'e} Avet-Loiseau and Cyrille Hulin and Thierry Facon",
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journal = "New England Journal of Medicine",
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T1 - Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma

AU - FIRST Trial Team

AU - Benboubker, Lotfi

AU - Dimopoulos, Meletios A.

AU - Dispenzieri, Angela

AU - Catalano, John

AU - Belch, Andrew R.

AU - Cavo, Michele

AU - Pinto, Antonello

AU - Weisel, Katja

AU - Ludwig, Heinz

AU - Bahlis, Nizar

AU - Banos, Anne

AU - Tiab, Mourad

AU - Delforge, Michel

AU - Cavenagh, Jamie

AU - Geraldes, Catarina

AU - Lee, Je Jung

AU - Chen, Christine

AU - Oriol, Albert

AU - De La Rubia, Javier

AU - Qiu, Lugui

AU - White, Darrell J.

AU - Binder, Daniel

AU - Anderson, Kenneth

AU - Fermand, Jean Paul

AU - Moreau, Philippe

AU - Attal, Michel

AU - Knight, Robert

AU - Chen, Guang

AU - Van Oostendorp, Jason

AU - Jacques, Christian

AU - Ervin-Haynes, Annette

AU - Avet-Loiseau, Hervé

AU - Hulin, Cyrille

AU - Facon, Thierry

PY - 2014/9/4

Y1 - 2014/9/4

N2 - Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. Conclusions: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.

AB - Background: The combination melphalan-prednisone-thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods: We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide-dexamethasone versus MPT. Results: The median progression-free survival was 25.5 months with continuous lenalidomide-dexamethasone, 20.7 months with 18 cycles of lenalidomide-dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide-dexamethasone vs. MPT and 0.70 for continuous lenalidomide-dexamethasone vs. 18 cycles of lenalidomide-dexamethasone; P<0.001 for both comparisons). Continuous lenalidomide-dexamethasone was superior to MPT for all secondary efficacy end points, including overall survival (at the interim analysis). Overall survival at 4 years was 59% with continuous lenalidomide-dexamethasone, 56% with 18 cycles of lenalidomide-dexamethasone, and 51% with MPT. Grade 3 or 4 adverse events were somewhat less frequent with continuous lenalidomide-dexamethasone than with MPT (70% vs. 78%). As compared with MPT, continuous lenalidomide-dexamethasone was associated with fewer hematologic and neurologic toxic events, a moderate increase in infections, and fewer second primary hematologic cancers. Conclusions: As compared with MPT, continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.

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