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 White, Daniel 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, 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 White, Daniel 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

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 = 535), Rd18 (n = 541), or MPT (n = 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 = .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.

Conflict of interest statement

Conflict-of-interest disclosure: T.F. reports advisory board fees from Amgen, Celgene, Janssen, Karyopharm, Pharmamar, and Takeda and speakers bureau fees from Amgen, Celgene, Janssen, and Takeda; M.A.D. reports honoraria and consulting/advisory fees from Amgen, Celgene, Janssen, and Takeda; A.D. reports grants from Alnylam, Celgene, Pfizer, Prothena, and Takeda; M.C. reports honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda; A. Pinto reports honoraria from Celgene, Spectrum, and Takeda and research funding from Takeda; K.W. reports research funding from Celgene and Janssen and honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Onyx, and Takeda and advisory board membership for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Onyx, and Takeda; H.L. reports consulting or advisory fees and speakers bureau fees from Amgen, Bristol-Myers Squibb, Celgene, and Janssen and research funding from Takeda; N.J.B. reports honoraria, consulting, or advisory fees and travel expenses from Amgen, Celgene, Janssen, and Takeda and research funding and fees for expert testimony from Celgene and Janssen; M.D. reports research grants, consultancy fees, and speaker’s honoraria from Celgene and Janssen, consultancy fees and speaker’s honoraria from Amgen, and consultancy fees from Bristol-Myers Squibb and Takeda; C.G. reports honoraria from and advisory board membership for Amgen, Bristol-Myers Squibb, Celgene, and Janssen; C.C. reports consulting for and research funding and honoraria from Celgene; A.O. reports advisory board fees from Amgen and Janssen; D.W. reports grants from Celgene and grants and personal fees from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, and Takeda; K.C.A. reports advisory board fees from Bristol-Myers Squibb, Celgene, Gilead, and Millennium; P.M. reports honoraria from Bristol-Myers Squibb, Celgene, Janssen, and Takeda; A. Perrot reports honoraria and consulting fees from Amgen, Celgene, Janssen, Novartis, and Takeda; M.R. reports grants, personal fees, and nonfinancial support from Amgen, Celgene, and Janssen; E.B. reports advisory board fees from Celgene; M.M. reports personal fees from Celgene; A.E.-H. reports employment and stock options from Celgene; G.C. reports employment, stock options, and travel expenses from Celgene; V.H. reports employment from Celgene; L.B. reports grants, personal fees, and nonfinancial support from Celgene and Janssen, personal fees and nonfinancial support from Amgen, and personal fees from Takeda; C.H. reports honoraria from Celgene; the remaining authors declare no competing financial interests.