Credit: CDC
In the phase 3 FIRST trial, a regimen of continuous lenalidomide and low-dose dexamethasone conferred the greatest progression-free survival (PFS) benefit among patients with newly diagnosed multiple myeloma (MM).
Patients who received this regimen had a significantly longer median PFS than patients who received a fixed course of lenalidomide plus low-dose dexamethasone or a combination of melphalan, prednisone, and thalidomide.
Results of this study appear in The New England Journal of Medicine. The research was previously presented at the 2013 ASH Annual Meeting. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.
Thierry Facon, MD, of Hôpital Claude Huriez in Lille, France, and his colleagues enrolled 1623 patients on this study. They were newly diagnosed with MM and not eligible for stem cell transplant.
Patients were randomized to receive lenalidomide and dexamethasone (Rd) in 28-day cycles until disease progression (n=535), to 18 cycles of lenalidomide and dexamethasone (Rd18) for 72 weeks (n=541), or to melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).
Response rates were significantly better with continuous Rd (75%) and with Rd18 (73%) than with MPT (62%, P<0.001 for both comparisons). Complete response rates were 15%, 14%, and 9%, respectively.
The median duration of response was 35.0 months with continuous Rd compared with 22.3 months for MPT (hazard ratio [HR]=0.63, P<0.001) and 22.1 months for Rd18 (HR=0.60, P<0.001).
The median time to disease progression was 32.5 months for patients receiving continuous Rd compared with 23.9 months (HR=0.68, P<0.001) for MPT and 21.9 months for Rd18 (HR=0.62, P<0.001).
The median PFS was 25.5 months with continuous Rd, 20.7 months with Rd18, and 21.2 months with MPT. This resulted in a 28% reduction in the risk of progression or death for patients treated with continuous Rd compared with those treated with MPT (HR=0.72, P<0.001) and a 30% reduction compared with Rd18 (HR=0.70, P<0.001).
The pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death for continuous Rd vs MPT (HR=0.78, P=0.02), but the difference did not cross the pre-specified superiority boundary (P<0.0096).
At the time of the analysis (May 24, 2013), 23% of patients in the continuous Rd arm were still on therapy.
Grade 3/4 adverse events that occurred in at least 8% of patients in the continuous Rd arm, Rd18 arm, or MPT arm included neutropenia (28%, 26%, 45%, respectively), anemia (18%, 16%, 19%), thrombocytopenia (8%, 8%,11%), febrile neutropenia (1%, 3%, 3%), leukopenia (5%, 6%, 10%), infection (29%, 22%, 17%), pneumonia (8%, 8%, 6%), deep vein thrombosis and/or pulmonary embolism (8%, 6%, 5%), asthenia (8%, 6%, 6%), fatigue (7%, 9%, 6%), and peripheral sensory neuropathy (1%, <1%, 9%).
Grade 3/4 cardiac disorders occurred in 12% of patients in the continuous Rd arm, 7% in the Rd18 arm, and 9% in the MPT arm.
The incidence of invasive second primary malignancies was 3% in patients taking continuous Rd, 6% in patients taking Rd18, and 5% in those taking MPT. The overall incidence of solid tumors was identical in the continuous Rd and MPT arms (3%) and 5% in the Rd18 arm.
