Final Results of a Phase 2 Study of Modified Lenalidomide, Bortezomib, and Dexamethasone (RVD lite) in Transplant-Ineligible Multiple Myeloma

PURPOSE: We sought a regimen that incorporates optimal novel agents in transplant-ineligible patients that balances efficacy with toxicity. Our study evaluated a 3-drug regimen of modified lenalidomide-bortezomib-dexamethasone (RVD lite) in this population.

METHODS: RVD lite was administered over a 35-day cycle. Lenalidomide 15 mg was given orally days 1-21; bortezomib 1.3 mg/m² once weekly subcutaneously (SC) on days 1, 8, 15, and 22; dexamethasone 20 mg orally day of and after bortezomib for 9 cycles followed by 6 cycles of consolidation. Eligibility requirements included ECOG performance status ≤ 2 and acceptable hepatic, renal, and hematologic function. Primary objective was to evaluate overall response rate (ORR). Secondary objectives included evaluation of safety, progression free survival (PFS), overall survival (OS), and the pharmacokinetic (PK) profile of intravenous (IV) and SC bortezomib.

RESULTS: Fifty-three eligible patients screened between 4/17/13 and 7/25/15; 50 received at least one dose of therapy. Median age at study entry was 73 years (range 65-91). ECOG performance status was 0 in 25 (50%), 1 in 18 (36%), and 2 in 7 (14 %) pts. ISS stage was I in 19 (38%), II in 17 (34%), and III in 14 (28%) pts. Fatigue was the most commonly reported toxicity occurring in 37 (74%), and was mostly grade 1 or 2 and manageable (19 (58%)). Other grade 3 or greater toxicities included hypophosphatemia in 17 (34%), neutropenia in 7 (14%), and rash in 5 (10%) pts. Peripheral neuropathy was reported in 33 (66%) patients with only 1 patient experiencing grade 3 neuropathy symptoms. The ORR was 91.4% in the 47 patients evaluable for response after 4 cycles of therapy. Seventy percent of evaluable patients achieved a very good partial response or better. Median PFS was 35.1 months (95% CI, 30.9 - ∞) and median OS not reached at a median follow-up of 30 months. PK data comparing IV and SC dosing showed no significant differences in plasma concentrations of bortezomib at 5 hours. Health-related quality of life showed statistically significant improvements in scores when compared to baseline in a subset of patients (n=30).

CONCLUSIONS: RVD lite is a well-tolerated and highly effective regimen in the transplant-ineligible population with robust PFS and OS. Our data demonstrates that we can bring the benefits of more effective combination strategies observed in younger, fitter, transplant-eligible patients to older, transplant-ineligible patients with modifications in dose and schedule, without compromising efficacy.