Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma

Thierry Facon, Meletios A. Dimopoulos, Angela Dispenzieri, John V. Catalano, Andrew Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar J. Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie D. Cavenagh, Catarina Geraldes, Je Jung Lee, Christine Chen, Albert Oriol, Javier De La Rubia, Darrell WhiteDaniel Binder, Jin Lu, Kenneth C. Anderson, Philippe Moreau, Michel Attal, Aurore Perrot, Bertrand Arnulf, Lugui Qiu, Murielle Roussel, Eileen Boyle, Salomon Manier, Mohamad Mohty, Herve Avet-Loiseau, Xavier Leleu, Annette Ervin-Haynes, Guang Chen, Vanessa Houck, Lotfi Benboubker, Cyrille Hulin

Research output: Contribution to journalArticle

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Abstract

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ‡60 months’ follow-up). Patients were randomized to Rd continuous (n 5 535), Rd18 (n 5 541), or MPT (n 5 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P 5 .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an 30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39.

Original languageEnglish (US)
Pages (from-to)301-310
Number of pages10
JournalBlood
Volume131
Issue number3
DOIs
StatePublished - Jan 18 2018

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Transplants
Survival Analysis
Multiple Myeloma
Hazards
Melphalan
Thalidomide
Prednisone
Dexamethasone
Survival
Therapeutics
Confidence Intervals
Standard of Care
Disease-Free Survival
Disease Progression
Bortezomib
Safety
lenalidomide
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. / Facon, Thierry; Dimopoulos, Meletios A.; Dispenzieri, Angela; Catalano, John V.; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J.; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D.; Geraldes, Catarina; Lee, Je Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C.; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille.

In: Blood, Vol. 131, No. 3, 18.01.2018, p. 301-310.

Research output: Contribution to journalArticle

Facon, T, Dimopoulos, MA, Dispenzieri, A, Catalano, JV, Belch, A, Cavo, M, Pinto, A, Weisel, K, Ludwig, H, Bahlis, NJ, Banos, A, Tiab, M, Delforge, M, Cavenagh, JD, Geraldes, C, Lee, JJ, Chen, C, Oriol, A, De La Rubia, J, White, D, Binder, D, Lu, J, Anderson, KC, Moreau, P, Attal, M, Perrot, A, Arnulf, B, Qiu, L, Roussel, M, Boyle, E, Manier, S, Mohty, M, Avet-Loiseau, H, Leleu, X, Ervin-Haynes, A, Chen, G, Houck, V, Benboubker, L & Hulin, C 2018, 'Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma', Blood, vol. 131, no. 3, pp. 301-310. https://doi.org/10.1182/blood-2017-07-795047
Facon, Thierry ; Dimopoulos, Meletios A. ; Dispenzieri, Angela ; Catalano, John V. ; Belch, Andrew ; Cavo, Michele ; Pinto, Antonello ; Weisel, Katja ; Ludwig, Heinz ; Bahlis, Nizar J. ; Banos, Anne ; Tiab, Mourad ; Delforge, Michel ; Cavenagh, Jamie D. ; Geraldes, Catarina ; Lee, Je Jung ; Chen, Christine ; Oriol, Albert ; De La Rubia, Javier ; White, Darrell ; Binder, Daniel ; Lu, Jin ; Anderson, Kenneth C. ; Moreau, Philippe ; Attal, Michel ; Perrot, Aurore ; Arnulf, Bertrand ; Qiu, Lugui ; Roussel, Murielle ; Boyle, Eileen ; Manier, Salomon ; Mohty, Mohamad ; Avet-Loiseau, Herve ; Leleu, Xavier ; Ervin-Haynes, Annette ; Chen, Guang ; Houck, Vanessa ; Benboubker, Lotfi ; Hulin, Cyrille. / Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. In: Blood. 2018 ; Vol. 131, No. 3. pp. 301-310.
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AU - Facon, Thierry

AU - Dimopoulos, Meletios A.

AU - Dispenzieri, Angela

AU - Catalano, John V.

AU - Belch, Andrew

AU - Cavo, Michele

AU - Pinto, Antonello

AU - Weisel, Katja

AU - Ludwig, Heinz

AU - Bahlis, Nizar J.

AU - Banos, Anne

AU - Tiab, Mourad

AU - Delforge, Michel

AU - Cavenagh, Jamie D.

AU - Geraldes, Catarina

AU - Lee, Je Jung

AU - Chen, Christine

AU - Oriol, Albert

AU - De La Rubia, Javier

AU - White, Darrell

AU - Binder, Daniel

AU - Lu, Jin

AU - Anderson, Kenneth C.

AU - Moreau, Philippe

AU - Attal, Michel

AU - Perrot, Aurore

AU - Arnulf, Bertrand

AU - Qiu, Lugui

AU - Roussel, Murielle

AU - Boyle, Eileen

AU - Manier, Salomon

AU - Mohty, Mohamad

AU - Avet-Loiseau, Herve

AU - Leleu, Xavier

AU - Ervin-Haynes, Annette

AU - Chen, Guang

AU - Houck, Vanessa

AU - Benboubker, Lotfi

AU - Hulin, Cyrille

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N2 - This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ‡60 months’ follow-up). Patients were randomized to Rd continuous (n 5 535), Rd18 (n 5 541), or MPT (n 5 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P 5 .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an 30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39.

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