Autologous stem cell transplant (ASCT) after a 3-drug induction regimen can prolong progression-free survival (PFS), compared with triplet induction alone, in patients with multiple myeloma (MM), according to results of a phase 3 trial presented at the 2022 ASCO Annual Meeting.1
Following lenalidomide, bortezomib, and dexamethasone (RVd) induction with ASCT and lenalidomide maintenance improved PFS, when compared with RVd induction and lenalidomide maintenance alone, explained study author Paul G. Richardson, MD, of Dana-Farber Cancer Institute in Boston.
With the phase 3 DETERMINATION trial (ClinicalTrials.gov Identifier: NCT01208662), Dr Richardson and colleagues sought to determine the effect of adding ASCT to RVd, followed by lenalidomide maintenance until disease progression.
The trial enrolled 722 patients, aged 18 to 65 years, with newly diagnosed MM. Dr Richardson noted that this trial has the highest African American participation of any phase 3 study in this setting to date (18.8%).
All patients received 3 cycles of RVd followed by stem cell collection (reserved for possible ASCT if disease progressed). Patients were then randomly assigned to receive 5 more cycles of RVd (RVd-alone arm, n=357) or melphalan at 200 mg/m2, followed by ASCT and 2 more cycles of RVd (RVd+ASCT arm, n=365). Patients in both arms received lenalidomide maintenance until disease progression or intolerable drug toxicity.
At a median follow-up of 76 months, the median PFS was significantly longer with RVd+ASCT. It was 46.2 months with RVd alone and 67.5 months with RVd+ASCT (hazard ratio [HR], 1.53; 95% CI, 1.23-1.91; P <.001).
Subsequent treatment was required for 79.6% of patients in the RVd-alone arm and 69.6% of those in the RVd+ASCT arm. Subsequent treatment included ASCT for 28% of patients in the RVd-alone arm.
Five-year overall survival rates were similar between the arms, at 79.2% with RVd-alone and 80.7% with RVd+ASCT (HR, 1.10; 95% CI, 0.73-1.65; P =.99).
The overall incidence of grade 3 or higher adverse events (AEs) was lower with RVd-alone than with RVd+ASCT (78.2% vs 94.2%), as was the incidence of grade 3 or higher hematologic AEs (60.5% vs 89.9%).
Secondary malignancies occurred in 10.4% of the RVd-alone arm and 10.7% of the RVd+ASCT arm. However, secondary acute myeloid leukemia/myelodysplastic syndrome was significantly higher with RVd+ASCT (0% vs 10%; P =.002).
Results from this study were also published in The New England Journal of Medicine.2
Disclosures: This research was supported, in part, by Celgene Corporation and Millennium Pharmaceuticals, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Richardson PG, Jacobus SJ, Weller E, et al. Lenalidomide, bortezomib, and dexamethasone (RVd) ± autologous stem cell transplantation (ASCT) and R maintenance to progression for newly diagnosed multiple myeloma (NDMM): the phase 3 DETERMINATION trial. Presented at ASCO 2022; June 3-7, 2022. Abstract LBA4.
- Richardson PG, Jacobus SJ, Weller E, et al. Triplet therapy, transplantation, and maintenance until progression in Myeloma. N Engl J Med. Published online June 5, 2022. doi:10.1056/NEJMoa2204925