Alessandra Larocca, MD, Ph.D. from the University of Torino, AOU S.Giovanni Battista, TORINO, Italy speaks about Dose/Schedule-Adjusted Rd-R vs Continuous Rd for elderly, intermediate-fit, newly diagnosed multiple myeloma patients.
Points to Remember
In intermediate-fit elderly NDMM, dose/schedule-adjusted Rd-R prolonged EFS while causing similar PFS and OS to normal continuous Rd.
For elderly multiple myeloma (MM) patients, lenalidomide-dexamethasone (Rd) is a common therapy. We compared the effectiveness and feasibility of a dose/schedule-adjusted Rd followed by maintenance 10 mg/day without dexamethasone (Rd-R) vs continuous Rd in elderly, intermediate-fit newly diagnosed MM patients in this randomized, phase III trial. The primary endpoint was event-free survival (EFS), which was characterized as progression/death for any reason, discontinuation of lenalidomide, and any hematologic or non-hematologic grade 4 or 3-4 adverse events (AEs). 101 of the 199 patients who were evaluated received Rd-R and 98 received continuous Rd. The average period of follow-up was 37 months. The best response rates were comparable: partial response rates in Rd-R vs continuous Rd groups were 78 percent vs 68 percent (p=0.15). Rd-R had an EFS of 10.4 months compared to 6.9 months with continuous Rd (HR 0.70, 95 percent CI 0.51-0.95, p=0.02). The median progression-free survival was 20.2 months vs 18.3 months (HR 0.78, 95 percent CI 0.55-1.10, p=0.16), and the 3-year average survival was 74% vs 63% (HR 0.62, 95 percent CI 0.37-1.03, p=0.06). In Rd-R vs Rd, the prevalence of at least one non-hematologic grade 3 AE was 33 percent vs 43 percent (p=0.14); the most common grade 3 AEs were neutropenia (21 percent vs 18 percent), infections (10 percent vs 12 percent), and skin disorders (7 percent vs 3 percent); constitutional and central nervous system AEs primarily linked to dexamethasone were more common with continuous Rd. In Rd-R vs Rd, respectively, lenalidomide was discontinued in 24 percent vs 30 percent of patients and decreased in 45 percent vs 62 percent of patients due to AEs. After 9 cycles of Rd, transitioning to reduced-dose lenalidomide maintenance without dexamethasone was possible in intermediate-fit patients, with comparable results to normal continuous Rd.