Abstract Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical
Background: Complement component 5 inhibitors (C5i) eculizumab and ravulizumab reduce thrombosis and organ damage, and improve survival for patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare hematologic disorder characterized by uncontrolled terminal complement activation. Some patients are mechanistically susceptible to extravascular hemolysis (EVH), which can be clinically significant (csEVH) and impact quality of life (QoL).
Aims: To report clinical trial and real-world prevalence of csEVH in patients with PNH who were clinically stable on C5i treatment, and to describe real-world physician-reported disease control and patient QoL, and physician- and patient-reported treatment satisfaction.
Methods: Clinical trial data from study 302 (NCT03056040) and real-world data from the multinational PNH Adelphi Disease Specific Programme™ (DSP) were used to describe the prevalence of csEVH. In study 302, C5i-experienced patients with PNH were randomized to receive eculizumab or ravulizumab for up to 26 weeks. Real-world prevalence and patient data were collected from the PNH DSP™, a cross-sectional survey of hematologists and oncologists and their consulting patients with PNH from December 2021 to July 2022. Data included patient demographics, symptoms, laboratory values, disease control, and treatment satisfaction. Because there is no universal definition for csEVH, study 302 defined csEVH as symptomatic anemia (hemoglobin [Hb] levels ≤ 9.5 g/dL) with absolute reticulocyte count ≥ 120 × 109/L, and with or without blood transfusion; based on the available real-world data from the PNH DSP™, including patient-reported outcomes, csEVH was defined as patients receiving a C5i for ≥ 3 months with Hb levels ≤ 9.5 g/dL and moderate/severe symptomatic fatigue, with or without a transfusion in the last 12 months. Descriptive statistics were performed.
Results: In study 302, csEVH prevalence in patients treated with eculizumab or ravulizumab was 21.3% (20/94) and 20.2% (19/94), respectively, irrespective of transfusion status. In the PNH DSP™, csEVH prevalence was 7.4% (15/202) and 7.8% (10/129) in patients treated with eculizumab or ravulizumab, respectively, irrespective of transfusion status. Study 302 demographics are published elsewhere. The PNH DSP™ patient demographics and results are presented in Table 1; in most patients with csEVH, physicians reported PNH was well controlled with eculizumab or ravulizumab (80.0% and 70.0%, respectively; Table 1). This was also observed in patients without csEVH (95.2% and 98.3%, respectively). The physician-reported patient QoL was ‘good–excellent’ in 53.4% and 60.0% of patients with csEVH treated with eculizumab or ravulizumab, respectively, and 78.6% and 80.7% in patients without csEVH, respectively (Table 1). For 86.7% and 80.0% of patients with csEVH, their physician was satisfied with eculizumab or ravulizumab, respectively (Table 1). Similarly, for most patients without csEVH, their physician was satisfied with eculizumab or ravulizumab (93.0% and 98.3%, respectively). Most patients were satisfied with C5i (with csEVH, 88.9%; without csEVH, 88.6%).
Summary/Conclusion: Clinical trial prevalence of csEVH (20.2–21.3%) in patients with stable PNH treated with C5i was substantiated by real-world physician-reported csEVH prevalence (7.4–7.8%). Despite csEVH, physicians reported that PNH was well controlled, and, in over half of patients, QoL was ‘good–excellent’; additionally, most patients were satisfied with C5i treatment.
Keywords: Paroxysmal nocturnal hemoglobinuria (PNH)