Lenalidomide and Dexamethasone for Multiple Myeloma Patients Superior to Standard of Care Regimen
New Orleans—After a median follow-up of 37 months, older patients with newly diagnosed multiple myeloma (MM) had a significant 28% reduction in disease progression or death if they received continuous treatment with lenalidomide plus low-dose dexamethasone compared with a standard regimen of melphalan, prednisone, and thalidomide for 72 weeks.
The results of the open-label, phase 3 trial could change the standard of care in this patient population, according to Thierry Facon, MD, lead author of the study, who presented the findings during a plenary session at the ASH meeting.
The study included 1623 patients at 246 centers in 18 countries who were ≥65 years of age or ineligible for stem cell transplantation. The median age was 73 years, and 35% of patients were >75 years of age. It was the largest registration study conducted for newly diagnosed MM patients and the first to enroll patients with renal insufficiencies. Celgene, the manufacturer of lenalidomide, sponsored the study.
“This population is somewhat close to a real life population,” Dr. Facon said.
Dr. Facon noted that the National Comprehensive Cancer Network recommends the use of thalidomide with melphalan and prednisone in this patient population. The safety profile of lenalidomide and low-dose dexamethasone was “manageable,” according to Dr. Facon, who added that hematological and nonhematological adverse events were “as expected.”
In the FIRST (Frontline Investigation of Rev/Dex Versus Standard Trial) trial, the authors randomized patients between August 2008 and March 2011 to receive lenalidomide plus low-dose dexamethasone until disease progression (n=535); lenalidomide and low-dose dexamethasone for 72 weeks (n=541); or melphalan, prednisone, and thalidomide for 72 weeks (n=547). Patients were from the United States, Canada, China, South Korea, Taiwan, Australia, New Zealand, and several European countries.
The median progression-free survival was 25.5 months for the continuous lenalidomide plus low-dose dexamethasone group compared with 21.2 months for patients receiving melphalan, prednisone, and thalidomide for 72 weeks (hazard ratio [HR], 0.72; P=.00006). The median progression-free survival was 20.7 months for patients taking lenalidomide and low-dose dexamethasone for 72 weeks. At 3 years, 42% of patients taking continuous lenalidomide and low-dose dexamethasone had no disease progression or death compared with 23% in each of the other groups. The progression-free survival benefit was consistent in a majority of subgroups, according to Dr. Facon.
The authors also conducted an interim analysis of overall survival when 35% of patients had died. The estimated, 4-year overall survival rates were 59% in the lenalidomide plus low-dose dexamethasone group and 51% in the melphalan, prednisone, and thalidomide group (HR, 0.78; P=.017).
In the past few years, studies have shown that combining thalidomide or bortezomib with melphalan plus prednisone is superior to melphalan plus prednisone in older MM patients who are ineligible for stem cell transplantation, according to Dr. Facon.
At the cut-off date of May 24, 2013, 23% of patients in the continuous lenalidomide plus low-dose dexamethasone group remained on treatment. No one in either of the other groups was still taking the medications. At week 72, 55% of patients in the continuous lenalidomide plus low-dose group, 52% of patients in the other lenalidomide and low-dose dexamethasone group, and 45% of patients in the melphalan, prednisone, and thalidomide remained on treatment. In addition, 39% of patients receiving continuous treatment with lenalidomide plus low-dose dexamethasone took the regimen for >2 years.
Furthermore, 11% of patients in the continuous lenalidomide plus low-dose dexamethasone group, 13% of patients in the 72-week lenalidomide plus low-dose dexamethasone, and 14% of patients in the melphalan, prednisone, and thalidomide group discontinued the study because of adverse events.
