Dose/Schedule-Adjusted Rd-R vs Continuous Rd for elderly, intermediate-fit, newly diagnosed multiple myeloma patients

Lenalidomide-dexamethasone (Rd) is a standard treatment for elderly multiple myeloma (MM) patients. In this randomized, phase III study, we investigated the efficacy 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. The primary endpoint was event-free survival (EFS), defined as progression/death for any cause, lenalidomide discontinuation, any hematologic grade 4 or non-hematologic grade 3-4 adverse events (AEs). Of the 199 evaluable patients, 101 received Rd-R and 98 continuous Rd. Median follow-up was 37 months. Best response rates were comparable: ≥ partial response rates were 78% vs 68% (p=0.15) in Rd-R vs continuous Rd groups. EFS was 10.4 with Rd-R vs 6.9 months with continuous Rd (HR 0.70, 95% CI 0.51-0.95, p=0.02). Median progression-free survival was 20.2 vs 18.3 months (HR 0.78, 95% CI 0.55-1.10, p=0.16), 3-year overall survival was 74% vs 63% (HR 0.62, 95% CI 0.37-1.03, p=0.06). At least 1 non-hematologic grade ≥3 AE rate was 33% vs 43% (p=0.14); the most frequent grade ≥3 AEs were neutropenia (21% vs 18%), infections (10% vs 12%) skin disorders (7% vs 3%) in Rd-R vs Rd; constitutional and central nervous system AEs mainly related to dexamethasone were more frequent with continuous Rd. Lenalidomide was discontinued for AEs in 24% vs 30% and was reduced in 45% vs 62% of patients, in Rd-R vs Rd, respectively. In intermediate-fit patients, switching to reduced-dose lenalidomide maintenance without dexamethasone after 9 cycles of Rd was feasible, with similar outcome to standard continuous Rd.