Continuous Lenalidomide/Low-Dose Dexamethasone Improves Survival vs Standard Treatment in Older Patients With Newly Diagnosed Myeloma
First-line treatment of newly diagnosed multiple myeloma using continuous treatment with the doublet of lenalidomide (Revlimid) and low-dose dexamethasone was superior to standard triplet treatment with melphalan, prednisone, and thalidomide (Thalomid) for 72 weeks, according to initial results of the FIRST (Front-line Investigation of Revlimid + Dexamethasone vs Standard Thalidomide) trial presented during the Plenary Session at the 55th American Society of Hematology Annual Meeting and Exposition in New Orleans (Abstract 2).
Patients treated with lenalidomide/low-dose dexamethasone were 28% less likely to experience disease progression or death compared with those who received melphalan/prednisone/thalidomide, and lenalidomide/low-dose dexamethasone improved overall survival, response rates, and duration of response. Additionally, lenalidomide/low-dose dexamethasone appears to have a safety advantage over melphalan/prednisone/thalidomide by causing fewer secondary hematologic malignancies.
“Traditionally, newly diagnosed multiple myeloma patients have received short bursts of treatment, while continuous treatment was reserved for relapsed patients. However, we believe that these new results will help encourage more research on the efficacy and safety of continuous treatment for newly diagnosed patients to help maximize their chances for overall long-term survival,” stated lead author Thierry Facon, MD, of Services des Maladies du Sang, Hôpital Claude Huriez, CHRU Lille, France.
“For some patients with low-risk multiple myeloma, this continuous regimen could make this disease a manageable, chronic condition,” he stated.
Phase III Trial
The multicenter, open-label, phase III trial enrolled 1,623 newly diagnosed multiple myeloma patients who were ineligible for stem cell transplant due to age (ie, over age 65) or other reasons. Participants were randomly assigned to one of three arms: continuous lenalidomide/low-dose dexamethasone in 28-day cycles until disease progression; lenalidomide/low-dose dexamethasone for 18 cycles (72 weeks); or 12 42-day cycles of melphalan/prednisone/thalidomide (72 weeks).
Dose adjustments were permitted for adverse events. All patients received antithrombotic prophylaxis as part of the protocol.
Improved Survival
At a median follow-up of 37 months, the primary endpoint of progression-free survival comparing continuous lenalidomide/low-dose dexamethasone vs melphalan/prednisone/thalidomide for 72 weeks was reached, demonstrating a highly significant 28% reduction in risk of disease progression or death (P = .00006). Median progression-free survival was 25.5 months for continuous lenalidomide/low-dose dexamethasone vs 21.2 months for melphalan/prednisone/thalidomide.
Median overall survival was also significantly better for continuous lenalidomide/low-dose dexamethasone vs lenalidomide/low-dose dexamethasone for 18 cycles: 25.5 vs 20.7 months (P = .00001). In addition, continuous lenalidomide/low-dose dexamethasone led to improvement in the overall survival rate at 4 years (59% vs 51.4% for melphalan/prednisone/thalidomide). The 4-year median survival rate in patients receiving lenalidomide/low-dose dexamethasone for 18 cycles was 55.7%.
Secondary Endpoints
Continuous lenalidomide/low-dose dexamethasone achieved consistent improvement over melphalan/prednisone/thalidomide for all secondary endpoints. Overall response rates (partial response or better) were 75% vs 62% (P < .00001), respectively, favoring continuous lenalidomide/low-dose dexamethasone.
The safety profiles of the two treatment arms were similar, with numerically fewer hematologic side effects in the doublet arm, as well as fewer hematologic malignancies.
For full disclosures of the study authors, view the study abstract on the ASH website.
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