Abstract
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a potentially life-threatening acquired hematopoietic stem cell disorder, resulting in anemia, hemoglobinuria, and acquired thrombophilia. Patients with PNH can experience a variety of disease-related symptoms, particularly fatigue, that can negatively impact their day-to-day functioning and health-related quality of life. In the Phase I/II COMPOSER trial (NCT03157635), patients with PNH who were treatment-naive or switched from eculizumab were treated with crovalimab, a novel anti-C5 monoclonal antibody designed with Sequential Monoclonal Antibody Recycling Technology (Röth et al. Blood 2020). Aims: To explore the efficacy of crovalimab from the perspective of patients with PNH using patient-reported outcome (PRO) tools to assess fatigue, functioning, and global health status (GHS)/quality of life (QoL). Methods: COMPOSER included treatment-naive (Parts 2 and 4 Arm A [4A]) and switched (Parts 3 and 4 Arm B [4B]) patients who received different crovalimab dosing regimens for a 20-week treatment period (Figure). Paper PROs were completed at baseline and at scheduled visits during the treatment period (up to Week 10 for Part 2 and Week 20 for Parts 3 and 4). Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale. Additional symptoms, functioning, and GHS/QoL were assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Results: The PRO completion rate at baseline was 100% of evaluable patients for Parts 2 (n=10), 3 (n=19), and 4A (n=8), and 86% for 4B (n=7). Completion rates remained ≥86% for all follow-up visits. Mean FACIT-Fatigue scores at baseline among treatment-naive patients in Parts 2 (29.7, standard deviation [SD]=13.7) and 4A (33.9, SD=8.7) were below or within the range for severe fatigue (30-34; Eek et al. J Patient Rep Outcomes 2021). Mean scores improved while on treatment with crovalimab, from baseline to Week 10 in Part 2 patients (8.8, SD=10.2) and to Week 20 in Part 4A patients (6.0, SD=6.1), exceeding the threshold for clinically meaningful improvement (5 points; Cella et al. ASH 2021). Switched patients in Parts 3 and 4B had less fatigue on average at baseline (37.3, SD=12.6; 37.0, SD=9.9, respectively) compared with treatment-naive patients, and showed largely minor changes at each follow-up. Similar results were observed for the EORTC QLQ-C30 Fatigue scale. Part 2 and Part 4A patients by Week 10 and 20, respectively, had mean fatigue severity levels comparable to (FACIT-Fatigue) or lower than (EORTC QLQ-C30 Fatigue) mean baseline values in switched patients. Mean EORTC QLQ-C30 scores in all functioning domains (i.e., physical, role, social, emotional, and cognitive) improved from baseline to Week 10 in Part 2 patients. Improvements in physical, role, and social functioning only were observed in Part 4A patients at all scheduled follow-up visits. Patients in both treatment-naive cohorts exhibited improvements in GHS/QoL. Switched patients, on average, exhibited limited change from baseline in EORTC QLQ-C30 scores, with mean improvements only observed for emotional functioning in Part 4B patients. Image:Summary/Conclusion: Treatment-naive patients experienced improvements from baseline in fatigue, functioning, and GHS/QoL whereas switched patients maintained baseline levels. These data provide supportive evidence for the treatment efficacy of crovalimab from the patient perspective.
Published Version
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