Daratumumab (DARA) + bortezomib/lenalidomide/dexamethasone (VRd) in transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM): Analysis of minimal residual disease (MRD) in the PERSEUS trial.

Paula Rodríguez-Otero Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona, Spain info_outline Paula Rodríguez-Otero, Philippe Moreau, Meletios Athanasios Dimopoulos, Meral Beksac, Aurore Perrot, Annemiek Broijl, Francesca Gay, Roberto Mina, Niels W.C.J. van de Donk, Fredrik Schjesvold, Michel Delforge, Hermann Einsele, Andrew Spencer, Sarah Lonergan, Diego Vieyra, Anna Sitthi-Amorn, Robin L. Carson, Joan Blade, Mario Boccadoro, Pieter Sonneveld

Authors Paula Rodríguez-Otero Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona, Spain info_outline Paula Rodríguez-Otero, Philippe Moreau, Meletios Athanasios Dimopoulos, Meral Beksac, Aurore Perrot, Annemiek Broijl, Francesca Gay, Roberto Mina, Niels W.C.J. van de Donk, Fredrik Schjesvold, Michel Delforge, Hermann Einsele, Andrew Spencer, Sarah Lonergan, Diego Vieyra, Anna Sitthi-Amorn, Robin L. Carson, Joan Blade, Mario Boccadoro, Pieter Sonneveld Organizations Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona, Spain, Hematology Department, University Hospital Hôtel-Dieu, Nantes, France, National and Kapodistrian University of Athens, Athens, Greece, Ankara University, Ankara, Turkey, CHU de Toulouse, IUCT-O, Université de Toulouse, UPS, Service d’Hématologie, Toulouse, France, Erasmus MC Cancer Institute, Rotterdam, Netherlands, Division of Hematology 1, AOU Città della Salute e della Scienza di Torino, and Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy, Department of Hematology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, Oslo Myeloma Center, Department of Hematology, and KG Jebsen Center for B-cell Malignancies, University of Oslo, Oslo, Norway, University of Leuven, Leuven, Belgium, Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany, Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, VIC, Australia, Janssen Research & Development, LLC, Spring House, PA, Hospital Clínic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain, Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy Abstract Disclosures Research Funding European Myeloma Network in collaboration with Janssen Research & Development, LLC Background: In the primary analysis of the phase 3 PERSEUS study, subcutaneous DARA (DARA SC) + VRd (D-VRd) induction/consolidation (ind/consol) and D-R maintenance improved progression-free survival (PFS) and increased depth of response (complete response or better [≥CR] and MRD negativity [neg]) compared to VRd ind/consol and R maintenance for TE NDMM. Here, we report further results on deepening of response and MRD neg during maintenance. Methods: TE pts with NDMM were randomized 1:1 to D-VRd or VRd. Pts in both arms received up to six 28-day cycles (4 pre-ASCT ind, 2 post-ASCT consol) 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 (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 + recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; Halozyme]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W during maintenance until PD. MRD-neg rate (clonoSEQ) was defined as the proportion of ITT pts who achieved both ≥CR and MRD neg. Results: In the 709 pts randomized (D-VRd, n=355; VRd, n=354), responses deepened over time with D-VRd vs VRd, including rates of ≥CR (end of consol: 44.5% vs 34.7%; P= 0.0078 and overall: 87.9% vs 70.1%; P<0.0001). MRD-neg rates increased over time and were higher with D-VRd vs VRd at 12, 24, and 36 mo after Cycle 1 Day 1 (all P<0.0001; Table). Rates of sustained MRD neg for ≥12 mo were higher for D-VRd vs VRd (10–5: 64.8% vs 29.7%; P<0.0001; 10–6: 47.3% vs 18.6%; P<0.0001); results were consistent across prespecified clinically relevant subgroups. Among pts who were MRD positive (pos) at end of consol, significantly higher proportions of pts in the D-VRd group vs the VRd group achieved MRD neg during maintenance at 10–5 (68.8% vs 52.7%; P= 0.0330) and 10–6 (62.3% vs 31.0%; P<0.0001) and sustained MRD neg for ≥12 mo at 10–5 (44.2% vs 22.6%; P= 0.0028) and 10–6 (34.4% vs 12.7%; P<0.0001).End of consol and overall MRD neg at both 10–5 and 10–6 were associated with improved PFS. Additional data on response rates in different study phases and sustained MRD neg will be presented. Conclusions: During maintenance, a greater proportion of pts with MRD-pos status achieved MRD neg with D-R vs R. The higher rates of deep (10–6) and sustained MRD neg achieved with D-VRd ind/consol and D-R maintenance vs VRd ind/consol and R maintenance translated to a clinically meaningful benefit of improved PFS. These data further support D-VRd and D-R maintenance as a new standard of care for TE pts with NDMM and highlight the benefit of DARA SC in maintenance. Clinical trial information: NCT03710603. 10–5 10–6 D-VRd (n = 355) VRd (n = 354) P D-VRd (n = 355) VRd (n = 354) P Rates of MRD neg up to: 12 mo 65.1% 38.7% <0.0001 43.9% 20.9% <0.0001 24 mo 72.1% 44.9% <0.0001 57.7% 27.4% <0.0001 36 mo 74.6% 46.9% <0.0001 63.9% 30.8% <0.0001

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