Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial

N J Bahlis, A Corso, L-O Mugge, Z-X Shen, P Desjardins, A-M Stoppa, O Decaux, T de Revel, M Granell, G Marit, H Nahi, H Demuynck, S-Y Huang, S Basu, T H Guthrie, A Ervin-Haynes, J Marek, G Chen, T Facon, N J Bahlis, A Corso, L-O Mugge, Z-X Shen, P Desjardins, A-M Stoppa, O Decaux, T de Revel, M Granell, G Marit, H Nahi, H Demuynck, S-Y Huang, S Basu, T H Guthrie, A Ervin-Haynes, J Marek, G Chen, T Facon

Abstract

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.

Trial registration: ClinicalTrials.gov NCT00689936.

Conflict of interest statement

NJB received honoraria from Celgene, Janssen, Amgen, Onyx, BMS, consulting/advisory fees from Celgene, Janssen, Amgen, Onyx, speaker’s bureau, research funding and travel expenses for Celgene, Janssen; L-OM has received honoraria from Janssen-Cilag, BMS, Celgene, Novartis, consulting/advisory fees from Novartis, research funding from Celgene, travel expenses from Celgene, Novartis; PD has received consulting/advisory fees from and participated in speaker’s bureau for Celgene; A-MS has received honoraria from Celgene, Amgen Takeda, received consulting/advisory fees from Celgene, travel expenses from Janssen, BMS; OD has received honoraria from Celgene, Janssen, Siemens, Novartis, consulting/advisory fees from Celgene, Janssen, Takeda, research funding from Celgene, Janssen, BMS, Binding Site, Siemens and travel expenses from Celgene, Janssen and Siemens; MG consulting/advisory fees from Celgene, Janssen, BMS, research funding from Celgene, Janssen; GM has received travel expenses from Celgene, Janssen-Cilag, Binding Site; SB has received travel expenses from Takeda; TG reports employment for 21st Century Oncology, speaker’s bureau from BMS, Novartis, BI Pharmaceuticals; AE-H and JM are employees of and have stock ownership in Celgene; GC reports employment, stock options and travel expenses for Celgene and TF has received compensation for leadership, honoraria, advisory/consulting, speaker’s bureau and travel expenses from Celgene. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cumulative response by treatment month for patients who achieved VGPR or better as best response. (a) Patients in the Rd continuous arm. (b) Patients in the Rd18 arm. Percentage shown is for patients achieving VGPR or better in the current month.
Figure 2
Figure 2
Kaplan–Meier estimates of duration of response. (a) Patients who achieved CR. (b) Patients who achieved VGPR or better. (c) Patients who achieved PR or better.
Figure 3
Figure 3
Kaplan–Meier estimates of PFS. (a) Patients who achieved CR. (b) Patients who achieved VGPR or better. (c) Patients who achieved PR or better. (d) Patients who achieved no better than SD. NE indicates not estimable.
Figure 4
Figure 4
Kaplan–Meier estimates of OS. (a) Patients who achieved CR. (b) Patients who achieved VGPR or better. (c) Patients who achieved PR or better. (d) Patients who achieved no better than SD.

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