Phase 3 Randomized Study of Daratumumab (DARA) + Bortezomib, Lenalidomide, and Dexamethasone (VRd) Versus Vrd Alone in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Who Are Eligible for Autologous Stem Cell Transplantation (ASCT): Primary Results of the Perseus Trial

Introduction: DARA plus bortezomib, thalidomide, and dexamethasone (D-VTd) quadruplet therapy has shown clinical benefit versus VTd alone and is approved for transplant-eligible pts with NDMM. VRd induction followed by autologous stem cell transplant (ASCT), VRd consolidation, and lenalidomide (R) maintenance is also considered a standard of care for transplant-eligible NDMM. In the phase 2 GRIFFIN study, intravenous DARA combined with VRd (D-VRd) induction/consolidation followed by D-R maintenance improved depth of response and progression-free survival (PFS) versus VRd induction/consolidation and R maintenance in transplant-eligible pts with NDMM after >4 years of follow-up. The phase 3 PERSEUS study is evaluating subcutaneous DARA (DARA SC) in combination with VRd induction/consolidation followed by D-R maintenance versus VRd induction/consolidation and R maintenance in transplant-eligible NDMM. Here we report the primary analysis of PERSEUS. Methods: Pts with NDMM who were aged 18-70 years and eligible for high-dose therapy and ASCT were randomized 1:1 to D-VRd or VRd, stratified by International Staging System (ISS) stage and cytogenetic risk. All pts received up to six 28-day cycles (4 pre-ASCT induction, 2 post-ASCT consolidation) of VRd (V: 1.3 mg/m2 SC on Days [D] 1, 4, 8, 11; R: 25 mg PO on D 1-21; d 40 mg PO/IV on D 1-4, 9-12) followed by R maintenance therapy (10 mg PO on D 1-28 until progressive disease [PD]). Pts in the D-VRd arm also received DARA SC (DARA 1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology, Halozyme, Inc.]) weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks during maintenance until PD. The primary endpoint is PFS; key secondary endpoints include overall complete response or better (≥CR) rate, overall minimal residual disease (MRD)-negativity rate (10-5 threshold; clonoSEQ®), and overall survival. Response and disease progression were assessed using a computerized algorithm based on IMWG response criteria. Overall MRD-negativity rate was defined as the proportion of pts who achieved MRD negativity and ≥CR at any time. Results: 709 pts were randomized (D-VRd, n=355; VRd, n=354). Median (range) age was 60 (31-70) years; 14.8% had ISS stage III disease, and 21.7% had high cytogenetic risk (t[4;14], t[14;16], or del[17p]). At clinical cutoff, 314 pts in the D-VRd arm and 299 pts in the VRd arm had completed all 4 induction and 2 consolidation