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<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.

Disclosures

Sonneveld:Karyopharm: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Janssen: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; European Myeloma Network: Other: President; Oncopeptides: Patents & Royalties; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:SWIXX: Honoraria; BEIGENE: Honoraria; JANSSEN: Honoraria; BMS: Honoraria; GSK: Honoraria; TAKEDA: Honoraria; MENARINI: Honoraria; REGENERON: Honoraria; SANOFI: Honoraria; ASTRA ZENECA: Honoraria; AMGEN: Honoraria, Membership on an entity's Board of Directors or advisory committees. Boccadoro:GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding. Quach:Pfizer: Consultancy; Roche: Consultancy; Sanofi: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; GSK: Consultancy, Research Funding; AbbVie: Research Funding; Johnson & Johnson: Consultancy. Ho:Novartis: Other: Research support on medical writing. Beksac:BMS, Janssen, Takeda, Sanofi: Speakers Bureau; BMS, Takeda, Janssen, Menarini, Amgen, GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees. Leleu:Kite, A Gilead Company: Consultancy, Honoraria. Mangiacavalli:Menarini Stem Line: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; IRCCS Fondazione Policlinico San Matteo, Pavia: Current Employment; BMS: Consultancy, Honoraria. Perrot:Amgen: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Menarini Stemline: Honoraria. Belotti:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Menarini Stemline: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Broijl:BMS: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Johnson & Johnson: Honoraria, Speakers Bureau. Gay:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Mina:GSK: Honoraria; Takeda: Honoraria; BMS: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Johnson & Johnson: Consultancy, Honoraria, Speakers Bureau. Nijhof:Janssen: Speakers Bureau; BMS: Speakers Bureau. van de Donk:Merck: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees. Katodritou:Abbvie: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Karyopharm: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; GSK: Honoraria, Research Funding. Schjesvold:Pfizer: Other: Honoraria for lectures and educational material; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; Targovax: Research Funding; Amgen: Other: Honoraria for lectures and educational material; Skylite: Other: Honoraria for lectures and educational material; Daiichi Sankyo: Other: Honoraria for lectures and educational material; GSK: Consultancy, Honoraria, Research Funding; SkylineDx: Other: Honoraria for lectures and educational material; Schain: Other: Honoraria for lectures and educational material; Novartis: Other: Honoraria for lectures and educational material; Sanofi: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; Celgene: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; Takeda: Consultancy, Other: Honoraria for lectures and educational material; Janssen-Cilag: Consultancy, Other: Honoraria for lectures and educational material, Research Funding; Bristol Myers Squibb: Consultancy, Other: Honoraria for lectures and educational material; AbbVie: Consultancy, Other: Honoraria for lectures and educational material. Sureda Balari:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Other: Travel Expenses; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; GSK: Consultancy, Honoraria, Speakers Bureau; Takeda Pharmaceutical: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; Alexion: Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GETH-TC: Other: President; EBMT: Other: President. Rosiñol Dachs:Amgen: Honoraria, Other: Educational lectures; Sanofi: Honoraria, Other: Honoraria for lectures; GSK: Honoraria, Other: Honoraria for lectures; Janssen Pharmaceutica: Honoraria, Other: Honoraria for lectures and meeting travel support; BMS, Takeda, Pfizer, Menarini: Honoraria. Delforge:Amgen, BMS, GSJ, Janssen, Sanofi, Pfizer, Roche: Honoraria; Amgen, BMS, GSJ, Janssen, Sanofi, Pfizer, F. Hoffmann-La Roche Ltd: Consultancy; Sanofi: Consultancy, Honoraria; GSK: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; University Hospital Leuven: Consultancy, Honoraria. Roeloffzen:Abbvie: Other: Travel expenses; BMS: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Other: Travel expenses, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau. Einsele:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene/Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria; BMS: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Spencer:AbbVie: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hajek:Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; PharmaMar: Consultancy, Honoraria; Novartis: Consultancy, Research Funding. Liu:Johnson & Johnson Innovative Medicine: Current Employment. Wang:Janssen: Current Employment, Current holder of stock options in a privately-held company. van Brummelen:Janssen: Current Employment. Vanquickelberghe:Johnson & Johnson Research and Development: Current Employment, Current equity holder in publicly-traded company. Sitthi-Amorn:Janssen: Current Employment, Current equity holder in publicly-traded company. de Boer:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Carson:Janssen: Current Employment, Current holder of stock options in a privately-held company. Katz:Pfizer: Current holder of stock options in a privately-held company; Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Gries:Johnson & Johnson Pharmaceutical: Current Employment, Current equity holder in publicly-traded company. Song:Janssen: Current Employment, Current equity holder in publicly-traded company. Ho:Janssen: Consultancy. Rodríguez-Otero:Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Johnson & Johnson - Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Regeneron: Other: Honoraria for lectures; Roche: Consultancy; GSK: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Honoraria for lectures; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Kite Pharma: Membership on an entity's Board of Directors or advisory committees. Bladé:Celgene/Bristol Myers Squibb: Other: Honoraria for lectures; Amgen: Other: Honoraria for lectures; Janssen: Other: Honoraria for lectures; Sanofi: Other: Honoraria for lectures. Moreau:AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Roche, Sanofi: Consultancy, Honoraria.

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