According to results from a study published in Blood, the 3-drug combination of bortezomib, lenalidomide, and dexamethasone (VRD) as induction therapy prior to autologous stem cell transplant (ASCT) is highly effective at achieving and maintaining high-quality responses in patients with multiple myeloma (MM).
The findings came from the ongoing, open label, randomized, phase 3 PETHEMA/GEM2012 trial (ClinicalTrials.gov Identifier: NCT01916252), which was designed to compare transplant conditioning regimens (intravenous busulfan plus melphalan vs melphalan alone) in 458 patients who received VRD induction and consolidation for newly diagnosed, symptomatic MM.
The researchers focused on a secondary end point, depth of response (complete response [CR] and measurable residual disease [MRD]) throughout induction, ASCT, and consolidation, and evaluated safety during induction. Patients, who were 65 years or younger, were administered 6 cycles of VRD, with each 28-day cycle consisting of lenalidomide given from day 1 to 21; subcutaneous bortezomib given on days 1, 4, 8, and 11; and dexamethasone given on days 1 to 4 and 9 to 12.
After 6 induction cycles, the CR rate was 33.4% and undetectable MRD rates were 28.8% and 47.4% at median thresholds of 3 x 10-6 and 3 x 10-4, respectively. Over time, responses deepened; in patients who had started cycle 6, the rates of very good partial response or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. Similarly, the rates of undetectable MRD at a threshold of 3 x 10-6 increased from 28.8% after induction to 42.1% after transplant and 45.2% after consolidation.
During induction, neutropenia (12.9%) and infection (9.2%) were the most common grade 3 or higher treatment-emergent adverse events. The rate of grade 2 or higher peripheral neuropathy was 17.0% (grade 3, 3.7%; grade 4, 0.2%). Treatment was disctonued in 14 patients (3.1%), and 9 patients (2.0%) died due to treatment-emergent adverse events.
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Rosiñol L, Oriol A, Rios R, et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma [published online, October 17, 2019]. Blood. doi:10.1182/blood.2019000241