The combination of lenalidomide-dexamethasone (Rd) is a standard of care treatment regimen for elderly patients with multiple myeloma (MM). Unfortunately, MM has a 5-year survival rate of approximately 54%. Enrolling 199 patients, a phase III study has investigated a dose-adjusted schedule of Rd followed by a maintenance schedule of 10mg/day of lenalidomide without dexamethasone (Rd-R) (N= 101), comparing this regimen to continuous Rd (N= 98) in elderly, intermediate-fit newly diagnosed MM patients. The primary endpoint of this study was event-free survival (EFS), defined as progression or death of any cause, lenalidomide discontinuation or any haematologic grade 4 or non-haematologic grade 3/4 adverse events (AEs).
At a median follow-up of 37 months, responses were comparable between both groups. ≥ partial response rates were 78% vs. 68% for the Rd-R and continuous groups, respectively (P= 0.15). However, treatment with Rd-R provided a better EFS of 10.4 months, compared to 6.9 months in those treated with continuous Rd (HR[95%CI]: 0.70[0.51-0.95], P= 0.02). Despite this, median progression-free survival (PFS) was not significant between the two groups, at 20.2 vs. 18.3 months, respectively (HR[95%CI]: 0.78[0.55-1.10, P= 0.16). The 3-year overall survival was 74% and 63% (HR[95%CI]: 0.62[0.37-1.03], P= 0.06). The rate of non-haematologic grade ≥3 AEs was lower with Rd-R at 33% vs. 43% with continuous Rd (P= 0.14). The most common grade ≥3 AEs were neutropenia (21% vs. 18%), infections (10% vs. 12%) skin disorders (7% vs. 3%). Lenalidomide was discontinued due to AEs in 24% and 30% of patients in the Rd-R and continuous Rd groups. Similarly, lenalidomide dose was reduced in 45% and 62%, respectively.
For newly diagnosed elderly MM patients, switching to a reduced-dose lenalidomide maintenance schedule without dexamethasone after 6 cycles of Rd was feasible, with comparable survival and safety outcomes to continuous Rd.