Updated Outcomes and Impact of Age in FIRST Trial in Multiple Myeloma
As reported by Hulin et al in the Journal of Clinical Oncology, the updated findings in the phase III FIRST trial continue to show improved progression-free and overall survival with continuous lenalidomide (Revlimid) plus low-dose dexamethasone (Rd) vs melphalan, prednisone, and thalidomide (MPT) in patients with multiple myeloma ineligible for stem cell transplantation. The benefit was observed in patients aged > 75 years as well as in the overall population.
Study Details
In the trial, 1,623 patients with newly diagnosed disease were randomized to receive Rd until disease progression (Rd continuous, n = 535), Rd for 72 weeks (18 cycles, Rd18; n = 541), or MPT (n = 547) for 72 weeks. In total, 567 patients (35%) were older than age 75. These older patients were more likely than younger patients to have stage III disease and severe renal impairment.
The primary endpoint was progression-free survival, with the primary comparison between continuous Rd and MPT. The initial report from the trial showed that continuous Rd vs MPT was associated with improved progression-free survival (hazard ratio [HR] = 0.72, P < .001) and, on interim analysis, improved overall survival (HR = 0.78, P = .02).
Outcomes by Age
Median follow-up was 45.5 months for the current analysis. Continuous Rd vs MPT was associated with prolonged median progression-free survival overall (26.0 vs 21.9 months, HR = 0.69, P < .001); hazard ratios were 0.64 (28.1 vs 22.4 months, P < .001) in patients aged ≤ 75 years and 0.80 (20.3 vs 19.8 months, P = .084) in those aged > 75 years. Median overall survival was 58.9 vs 48.5 months (HR = 0.75, 95% confidence interval [CI] = 0.62–0.90), including 60.9 vs 55.3 months (HR = 0.76, 95% CI = 0.60–0.96) among those aged ≤ 75 years and 52.3 vs 37.8 months (HR = 0.72, 95% CI = 0.54–0.96) among those aged > 75 years.
Progression-free survival with Rd18 was similar to that with MPT, and overall survival with Rd18 was marginally inferior to that with continuous Rd (4-year rates 3% and 4% lower in patients aged ≤ 75 years and > 75 years).
Safety
Rates of grade 3 or 4 adverse events were similar for patients aged ≤ 75 and > 75 years receiving continuous Rd, including neutropenia (28% and 29%), anemia (18% and 19%), infection (30% and 29%), and cardiac disorders (12% and 12%). Lenalidomide dose reductions (44% vs 37%) and discontinuation (26% vs 21%) were more common in those aged > 75 years.
The investigators concluded: “Results support Rd continuous treatment as a new standard of care for stem-cell transplantation–ineligible patients with newly diagnosed MM of all ages.”
The study was supported by the Intergroupe Francophone du Myélome and Celgene Corporation.
Thierry Facon, MD, of the Centre Hospitalier Régional Universitaire de Lille, France, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
