Updated Results of a Phase 2 Study of Modified Lenalidomide, Bortezomib, and Dexamethasone (RVd-lite) in Transplant-Ineligible Multiple Myeloma
Authors: O'Donnell Elizabeth K. , Laubach Jacob P. , Yee Andrew J. , Redd Robert , Huff Carol Ann , Basile Frank , Wade Philip M. , Paba-Prada Claudia E. , Ghobrial Irene M. , Schlossman Robert L. , Burke Jill N. , Harrington Cynthia C. , Lively Kathleen J. , Lyons Hannah , Munshi Nikhil C. , Anderson Kenneth C. , Richardson Paul G. , Raje Noopur S. 
Published: November 2019

PURPOSE: This updated analysis examined survival outcomes after 60 months of follow-up in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with the 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 enrolled between 4/17/13 and 7/25/15; 50 received at least one dose of therapy. As previously reported, the median age at study entry was 72 years (range 65-91). 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 in 29 (58%). Other grade 3 or greater toxicities included hypophosphatemia in 17 (34%), neutropenia in 7 (14%), and rash in 5 (10%) pts. Low grade peripheral neuropathy was reported in 31 (62%) patients with only 1 patient experiencing grade 3 symptoms. There were statistically significant improvements in scores of physical functioning (p=0.013), future perspective (p=0.023) and disease symptoms (p=0.001). Patients reported fewer symptoms across all symptom domains with the exception of diarrhea. The ORR was 86% and 66% of patients achieved a very good partial response (VGPR) or better. The median time to response was 1.1 months. At a follow-up of 61 months, median PFS was 41.9 months (95% CI, 31.2 - ∞) and median OS not reached. The 5-year overall survival was 61.3%. Sixty-six percent of patients received lenalidomide maintenance.
CONCLUSIONS: RVD lite is a well-tolerated and highly effective regimen in the transplant-ineligible population with robust PFS and OS. Our data demonstrate that the benefits of more effective combination strategies observed in younger, fitter, transplant-eligible patients can be effectively used in older, transplant-ineligible patients with modifications in dose and schedule, without compromising efficacy.

Disclosures
O'Donnell: Celgene: Consultancy; Sanofi: Consultancy; BMS: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Yee:Takeda: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy; Karyopharm: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Amgen: Consultancy, Honoraria. Huff:Karyopharm, Sanofi, MiDiagnostics: Consultancy; Member of Safety Monitoring Board for Johnson and Johnson: Membership on an entity's Board of Directors or advisory committees. Schlossman:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Munshi:Celgene: Consultancy; Takeda: Consultancy; Abbvie: Consultancy; Janssen: Consultancy; Adaptive: Consultancy; Amgen: Consultancy; Oncopep: Consultancy. Anderson:Gilead Sciences: Other: Advisory Board; Janssen: Other: Advisory Board; Sanofi-Aventis: Other: Advisory Board; OncoPep: Other: Scientific founder ; C4 Therapeutics: Other: Scientific founder . Richardson:Bristol-Myers Squibb: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding. Raje:Merck: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Celgene Corporation: Consultancy; Amgen Inc.: Consultancy; Bristol-Myers Squibb: Consultancy.