Photo courtesy of Celgene
Updated trial results support continuous treatment with lenalidomide and low-dose dexamethasone (Rd) as a standard of care for patients of all ages who have newly diagnosed multiple myeloma (MM) and are ineligible for stem cell transplant, according to researchers.
In this phase 3 trial, patients who received continuous Rd (until disease progression) had better progression-free survival (PFS) and overall survival (OS) than patients who received 18 cycles of Rd (Rd18) or a combination of melphalan, prednisone, and thalidomide (MPT).
Updated results from this study, known as the FIRST trial, were published in the Journal of Clinical Oncology.
Results were previously published in NEJM in 2014. The study was supported by Intergroupe Francophone du Myélome and Celgene Corporation, the makers of lenalidomide.
Thierry Facon, MD, of Centre Hospitalier Regional Universitaire de Lille in France, and his colleagues enrolled 1623 patients on this trial. They were newly diagnosed with MM and not eligible for stem cell transplant.
Patients were randomized to receive Rd in 28-day cycles until disease progression (n=535), Rd18 for 72 weeks (n=541), or MPT for 72 weeks (n=547).
Response
In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.
The median duration of response was 32 months (range, 26-37) in the continuous Rd group, 22 months (range, 19-23) in the Rd18 group, and 22 months (range, 20-25) in the MPT group.
PFS and OS
The median PFS was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, the PFS rate was 33%, 14%, and 13%, respectively.
The hazard ratio (HR) for continuous Rd vs MPT was 0.69. The HR for continuous Rd vs Rd18 was 0.71. And the HR for Rd18 vs MPT was 0.99.
The median OS was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, the OS rate was 60%, 57%, and 51%, respectively.
The HR for continuous Rd vs MPT was 0.75. The HR for continuous Rd vs Rd18 was 0.91. And the HR for Rd18 vs MPT was 0.83.
Safety
The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.
Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.
Grade 3/4 peripheral sensory neuropathy was less frequent in the continuous Rd and Rd18 groups than the MPT group.
The incidence of invasive second primary malignancy was 4% in the continuous Rd group, 6% in the Rd18 group, and 6% in the MPT group.
