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