A new study published in Blood found that switching select older patients to a lower dose of lenalidomide and discontinuing dexamethasone after nine months was not only safe, but it also yielded similar outcomes as compared with patients who received continuous Rd.
Lenalidomide + dexamethasone (Rd) is a standard treatment for elderly multiple myeloma (MM) patients. Since older patients are more susceptible to adverse events, treatment interventions that might mitigate these are needed.
This randomized, phase III study, 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. The authors concluded that 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.Switching to 10 mg lenalidomide maintenance without dexamethasone after 9 cycles of Rd = better tolerability & unaltered outcomes (compared to continuous Rd) in elderly, intermediate-fit, newly diagnosed myeloma #mmsm @theMMRF @IMFmyeloma https://t.co/aRsb8nIuay
— Ola Landgren, M.D. (@DrOlaLandgren) March 22, 2021