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

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.

SUBMITTER: Facon T

PROVIDER: S-EPMC5774211 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Facon Thierry T Dimopoulos Meletios A MA Dispenzieri Angela A Catalano John V JV Belch Andrew A Cavo Michele M Pinto Antonello A Weisel Katja K Ludwig Heinz H Bahlis Nizar J NJ Banos Anne A Tiab Mourad M Delforge Michel M Cavenagh Jamie D JD Geraldes Catarina C Lee Je-Jung JJ Chen Christine C Oriol Albert A De La Rubia Javier J White Darrell D Binder Daniel D Lu Jin J Anderson Kenneth C KC Moreau Philippe P Attal Michel M Perrot Aurore A Arnulf Bertrand B Qiu Lugui L Roussel Murielle M Boyle Eileen E Manier Salomon S Mohty Mohamad M Avet-Loiseau Herve H Leleu Xavier X Ervin-Haynes Annette A Chen Guang G Houck Vanessa V Benboubker Lotfi L Hulin Cyrille C

Blood 20171117 3

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 presp ...[more]

PMID: 29150421

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Project description:Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide greater options to individualize treatment and help patients achieve a clinically meaningful response.

Dataset Information

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

Publications

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

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