Modified Lenalidomide, Bortezomib, and Dexamethasone (RVD-lite) Regimen for Transplant-Ineligible Patients with Newly Diagnosed MM

Multiple myeloma (MM) is primarily a disease of older adults, with a median age of 66 years at diagnosis. Based on results of the FIRST trial, the lenalidomide and dexamethasone (RD) regimen is considered the new standard of care in older, transplant-ineligible patients with newly diagnosed MM (NDMM).¹ To further optimize treatment outcomes for this patient population, the present study evaluated the triple combination of bortezomib plus RD (RVD) but delivered on a modified dose and schedule (RVD-lite) in older patients with transplant-ineligible MM.² The RVD-lite regimen consisted of a 35-day cycle of lenalidomide (15 mg, days 1-21) plus bortezomib (1.3 mg/m² weekly subcutaneously on days 1, 8, 15, and 22), and dexamethasone (20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 for patients ≤75 years, and days 1, 8, 15, and 22 for those ≥75 years); bortezomib was administered intravenously in cycle 1 for the first 10 patients and subcutaneously thereafter.

A total of 53 NDMM patients were enrolled in the study; the median age at diagnosis was 72 years. The majority (n = 49) of patients experienced treatment-related toxicities; most common toxicities included fatigue (63%) and peripheral neuropathy (PN) of any grade (43%). Fatigue and PN were mostly of grade 1/2 severity. Grade 3/4 toxicities included hypophosphatemia (31%), rash (10%), and PN (2%).

Among the 40 patients who were evaluable for efficacy after 4 cycles, the investigator-reported overall response rate was 90%, including 10 (25%) complete responses, 14 (35%) very good partial responses, and 12 (30%) partial responses. Three patients discontinued treatment after <1 cycle, 1 due to worsening adrenal insufficiency, 1 due to lenalidomide treatment-related rash, and 1 at the investigator’s discretion. Pharmacokinetic analysis showed that plasma concentrations of bortezomib were similar between intravenous and subcutaneous dosing. At median follow-up of 17.2 months in 48 evaluable patients, the 1-year progression-free survival (PFS) was 95% and 2-year PFS was 68%; median overall survival has not been reached. Based on these results, the authors concluded that modified RVD (RVD-lite) was a well-tolerated and highly effective regimen in older transplant-ineligible patients with NDMM.

1. Benboubker L, et al. N Engl J Med. 2015;371(10):906-917.
2. O’Donnell EK, et al. ASH 2015. Abstract 4217.