A phase 2 study of modified lenalidomide, bortezomib and dexamethasone in transplant‐ineligible multiple myeloma

Abstract

We sought a regimen that incorporates optimal novel agents in transplant-ineligible patients that balances efficacy with toxicity. Our study evaluated modified lenalidomide-bortezomib-dexamethasone (RVD lite) in this population. RVD lite was administered over a 35-day cycle. Lenalidomide 15 mg was given orally days 1–21; bortezomib 1.3 mg/m2 weekly subcutaneously (SC) on days 1, 8, 15, and 22; and dexamethasone 20 mg orally day of and after bortezomib for 9 cycles followed by 6 cycles of consolidation with lenalidomide and bortezomib. Primary objective was to evaluate overall response rate (ORR). Secondary objectives included safety, progression free survival (PFS), and overall survival (OS). Fifty-three eligible patients screened between 4/17/13 and 5/20/15; 50 received at least one dose of therapy. Median age at study entry was 73 years (range 65–91). The ORR was 86% and 66% of patients achieved a very good partial response (VGPR) or better. Median PFS was 35.1 months (95% CI, 30.9 - ∞) and median OS was not reached at a median follow-up of 30 months. Peripheral neuropathy was reported in 31 (62%) patients with only 1 patient experiencing grade 3 symptoms. RVD lite is a well-tolerated and highly effective regimen in the transplant-ineligible population with robust PFS and OS.

Venous thromboembolism risk with contemporary lenalidomide‐based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta‐analysis

“…This forest plot illustrates the percentage of events per 100 patient‐cycles for respective therapies. BPR indicates bendamustine, prednisone, and lenalidomide; CPR, cyclophosphamide, prednisone, and lenalidomide; HDACi, histone deacetylase inhibitor; MoAB, monoclonal antibody; MPR, melphalan, prednisone, and lenalidomide; mTORi, mammalian target of rapamycin inhibitor; PI, proteasome inhibitor; R, lenalidomide; Rd, lenalidomide and low‐dose dexamethasone …”

Lenalidomide‐based response‐adapted therapy for older adults without high risk myeloma

“…As expected, older adults and, specifically, patients over the age of 75 years had a median PFS of 20 months with lenalidomide and dexamethasone; indeed, patient age over 65 years was associated with reduced PFS and overall survival on multivariate analyses (Durie et al , ). More recently, O'Donnell et al () reported on a dose‐attenuated RVD regimen, named RVD lite, in a cohort of newly diagnosed patients who were ineligible for high‐dose therapy and stem‐cell transplantation and had a median age of 73 years. The ORR was 86%, and the median PFS was 35 months (O'Donnell et al , ).…”

“…More recently, O'Donnell et al () reported on a dose‐attenuated RVD regimen, named RVD lite, in a cohort of newly diagnosed patients who were ineligible for high‐dose therapy and stem‐cell transplantation and had a median age of 73 years. The ORR was 86%, and the median PFS was 35 months (O'Donnell et al , ). Ixazomib, an oral proteasome inhibitor, has also been combined with lenalidomide and dexamethasone among newly diagnosed myeloma patients, resulting in a high response rate and less neurotoxicity (Richardson et al , ).…”

Management of multiple myeloma in older adults: Gaining ground with geriatric assessment

“…4 Other combinations, such as a modified combination of weekly bortezomib, reduced-dose lenalidomide and dexamethasone (“RVD lite”), are being explored, with encouraging toxicity profiles. 53 Bortezomib-based regimens improve outcomes in older patients. Without a clearly superior regimen, treatment choice may be based on patient- and disease-related factors rather than expected response.…”