Health-Related Quality of Life in Transplant-Eligible Patients with Newly Diagnosed Multiple Myeloma: Data from the Perseus Trial of Subcutaneous Daratumumab Combined with Bortezomib, Lenalidomide, and Dexamethasone (D-VRd)
Authors: Sonneveld Pieter , Dimopoulos Meletios A. , Boccadoro Mario , Quach Hang , Ho Phoebe Joy , Beksac Meral , Hulin Cyrille , Antonioli Elisabetta , Leleu Xavier , Mangiacavalli Silvia , Perrot Aurore , Cavo Michele , Belotti Angelo , Broijl Annemiek , Gay Francesca , Mina Roberto , Nijhof Inger S. , van de Donk Niels W.C.J. , Katodritou Eirini , Schjesvold Fredrik , Sureda Balari Anna , Rosiñol Dachs Laura , Delforge Michel , Roeloffzen Wilfried , Driessen Christoph , Vangsted Annette , Einsele Hermann , Spencer Andrew , Hajek Roman , Jurczyszyn Artur , Lonergan Sarah , Liu Yanfang , Wang Jianping , van Brummelen Emilie M.J. , Vanquickelberghe Veronique , Sitthi-Amorn Anna , de Boer Carla J. , Carson Robin , Katz Eva G. , Gries Katharine S. , Song Jiaqi , Ho Kai Fai , Rodríguez-Otero Paula , Bladé Joan , Moreau Philippe 
Published: December 2024

Introduction: In the phase 3 PERSEUS trial (NCT03710603), the addition of subcutaneous (SC) daratumumab (D) to bortezomib, lenalidomide, and dexamethasone (VRd) induction and consolidation therapy and to lenalidomide (R) maintenance therapy conferred clinically meaningful benefits on progression-free survival (PFS; hazard ratio, 0.42; 95% CI, 0.30-0.59; P&lt;0.001; median not reached in both arms, 48-month PFS, 84.3% vs 67.7%) and was well tolerated with manageable side effects in transplantation-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM) . In addition to prolonging survival, maintaining health-related quality of life (HRQoL) is an important treatment goal for patients with MM. In the current analysis, HRQoL (a secondary endpoint of the PERSEUS trial) was evaluated.

Methods: TE patients with NDMM were randomized to receive SC D combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd-DR group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd-R group) . Questionnaires completed by patients included the European Organisation for Research and Treatment of Cancer QoL questionnaire core 30 (EORTC QLQ-C30), from which global health status (GHS), physical functioning, pain, and fatigue scales are reported; the disease symptoms scale from the EORTC Multiple Myeloma module QoL questionnaire (QLQ-MY20); and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) visual analog scale (VAS). Each scale has a score range of 0-100, with higher scores indicating better functioning for GHS, physical functioning, and VAS, and lower scores indicating fewer symptoms for pain, fatigue, and disease symptoms. Responder analyses used a 10-point threshold for EORTC scales and 7 points for EQ-5D-5L VAS to define clinically meaningful improvement/worsening.

Results: Baseline characteristics were well balanced between the D-VRd-DR (N=355) and VRd-R (N=354) arms of the study (intent-to-treat population). At the time of clinical cut-off, median follow-up was 47.5 months. At maintenance cycle 34 (MC34), 254 patients in the D-VRd-DR group and 164 patients in the VRd-R group remained on study. Compliance with the questionnaires was high in both arms at baseline (D-VRd-DR vs VRd-R: EORTC QLQ-C30, 95.5% vs 94.1%; EORTC-MY-20, 94.9% vs 93.8%; EQ-5D-5L VAS, 94.4% vs 94.1%) and remained high throughout MC34 day 1 (D-VRd-DR vs VRd-R: EORTC QLQ-C30, 77.6% vs 75.0%; EORTC-MY-20, 77.6% vs 75.6%; EQ-5D-5L VAS, 77.6% vs 75.6%). Patients treated with D-VRd-DR experienced HRQoL improvement from baseline (before induction) that was apparent by the time maintenance began and was sustained through MC34 day 1 (Least Squares [LS] mean change from baseline to MC34 for EORTC QLQ-C30, GHS 6.99, physical functioning 9.30, pain -14.94, fatigue -8.71; EORTC-MY-20 disease symptoms, -10.17; EQ-5D-5L VAS, 9.4) and was comparable with VRd-R (LS means for EORTC QLQ-C30, GHS 4.94, physical functioning 9.87, pain -12.93, fatigue -8.90; EORTC-MY-20 disease symptoms, -9.31; EQ-5D-5L VAS, 8.6). Proportions of patients with clinically meaningful improvements in HRQoL at each cycle up to MC34 were similar across treatment arms (D-VRd-DR vs VRd-R: EORTC QLQ-C30, GHS 37.8% vs 36.8%, physical functioning 39.5% vs 41.1%, pain 48.9% vs 50.0%, fatigue 46.5% vs 53.1%; EORTC-MY-20 disease symptoms, 47.3% vs 49.1%; EQ-5D-5L VAS, 49.7% vs 43.9%).

Conclusions: Quadruplet therapy with D-VRd-DR provides durable improvements in overall HRQoL, MM symptoms, and functioning. These data are consistent with the efficacy and safety of D-VRd-DR. HRQoL improvements are comparable to those seen with VRd-R, indicating no detriment to HRQoL with the addition of D during induction, consolidation, and maintenance phases. Together with favorable efficacy outcomes data, these data support D-VRd-DR as a new standard of care for TE NDMM.