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)

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.

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Journal
Blood
Published
2024-11-05
DOI
https://doi.org/10.1182/blood-2024-201630
Primary Topic
Multiple Myeloma Research and Treatments
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article
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article

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)

Andrew Spencer, Pieter Sonneveld, Roberto Mina, Wilfried W. H. Roeloffzen et al.
Blood
Multiple Myeloma Research and Treatments
article

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)

Andrew Spencer, Pieter Sonneveld, Roberto Mina, Wilfried W. H. Roeloffzen, Phoebe Joy Ho, Véronique Vanquickelberghe, Kai Fai Ho, Hermann Einsele, Eva G. Katz, Mario Boccadoro, Christoph Driessen, Francesca Gay, Joan Bladé, Niels W.C.J. van de Donk, Meral Beksaç, Meletios Athanasios Dimopoulos, Eirini Katodritou, Silvia Mangiacavalli, Artur Jurczyszyn, Sarah Lonergan, Xavier P Leleu, Laura Rosiñol Dachs, Richard G. Carson, Katharine S. Gries, Emilie M.J. van Brummelen, Annemiek Broijl, Annette Juul Vangsted, Inger S. Nijhof, Michèle Cavo, Elisabetta Antonioli, Angelo Belotti, Anna Sureda, Anna Sitthi-Amorn, Fredrik Schjesvold, Paula Rodríguez‐Otero, Aurore Perrot, Cyrille Hulin, Roman Hájek, Hang Quach, Jianping Wang, Michel Delforge, Philippe Moreau, Yanfang Liu, Jiaqi Song, Carla J. de Boer
article en

Abstract

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.

BloodVol. 144(Supplement 1)
Jagiellonian University (PL), The University of Sydney (AU), University Medical Center Groningen (NL), Université Toulouse III - Paul Sabatier (FR), Janssen (Belgium) (BE), Inserm (FR), The University of Melbourne (AU), Université Fédérale de Toulouse Midi-Pyrénées (FR), University of Oslo (NO), University of Ostrava (CZ), National and Kapodistrian University of Athens (GR), University of St.Gallen (CH), Royal Prince Alfred Hospital (AU), Rigshospitalet (DK), Centre Hospitalier Universitaire de Toulouse (FR), Université de Poitiers (FR), Fundación Pethema (ES), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Institut d'Investigació Biomédica de Bellvitge (ES), St Vincent's Hospital Melbourne (AU), Theageneio General Hospital (GR), University Hospital Ostrava (CZ), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), St. Antonius Ziekenhuis (NL), Institut Català d'Oncologia (ES), Hospital Clínic de Barcelona (ES), Hôpital Cardiologique du Haut-Lévêque (FR), Istinye University (TR), Universitätsklinikum Würzburg (DE), Clinica Universidad de Navarra (ES), Global Services (Slovakia) (SK), Erasmus MC Cancer Institute (NL), Janssen (United States) (US), Policlinico San Matteo Fondazione (IT), Liv Hospital (TR), Janssen (Netherlands) (NL), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Alfred Health (AU), University of Florence (IT), Monash University (AU), Universitat de Barcelona (ES), Vrije Universiteit Amsterdam (NL), University of Bologna (IT), KU Leuven (BE)
Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Gilead Sciences, Alexion Pharmaceuticals, Celgene, F. Hoffmann-La Roche, Regeneron Pharmaceuticals, Adaptive Biotechnologies, SkylineDx, Servier, PharmaMar, Kite Pharma, Janssen Pharmaceuticals, Daiichi Sankyo Europe, Cilag
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