Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Treated with Pegcetacoplan: Real Life Experience

Introduction: C5 inhibitors (C5i) treatment has dramatically improved the management of intravascular hemolysis (IVH) in PNH patients. However, a significant proportion of patients remain anemic due to suboptimal control of IVH and the development of extravascular hemolysis (EVH), consequence of C5i treatment. Pegcetacoplan (PEG) is the first proximal inhibitor of the complement system, through the inhibition of C3, allowing to control both IVH and EVH. PEG has recently been marketed in Spain for use in adult PNH patients who remain anemic after treatment with an C5i for at least 3 months. The objective of this work is to analyze the response of the first patients treated with PEG in real life in Spain.

Patients and methods: clinical and analytical variables were collected from a series of 10 patients diagnosed with PNH who received treatment with PEG through an early access program. PEG was self-administered subcutaneously at 1080 mg twice a week. See Table 1. Transfusion needs and the adverse effects that occurred were also collected.

Results: median (range) duration of treatment with PEG at the time of the analysis was 4 (2-8) months. Hemoglobin (Hb) values increased a median of 2.4 g/dL after PEG treatment. This improvement was rapidly observed since the beginning of the treatment (median increase at 1 week was 1.3 g/dL and at 2 weeks 2.4 g/dL). All patients reached Hb levels of >8 g/dL, 80% >10 g/dL and 40% >12 g/dL. An increased in Hb >2 g/dL was observed in 60% of the patients. Median values of parameters of hemolysis (absolute reticulocyte counts, bilirubin, LDH) became normal. See Table 2. The direct antiglobulin test turned into negative in all positive cases pre-PEG (4 out of 4). No patient suffered from acute hemolytic events, thrombosis, or required PRBC transfusion once PEG had been initiated. On a 5-point scale (0: nothing; 5: very much), subjective improvement of patient quality of life and physician satisfaction were 4 (3-5), and 5 (3-5) [median (range)]. PEG-related adverse events were just reported in one patient (10%): mild post-infusion nausea. At the end of the analysis, all patients continue on PEG.

Conclusions: the results observed in the first patients treated with PEG in real life in Spain, although with a limited follow-up, confirm those reported in phase 3 clinical trials, with significant improvement in the Hb levels and hemolysis parameters, which results in transfusion independence. PEG was also shown to act quickly from the start of treatment, to significantly improve quality of life, and to present an excellent safety profile. PEG, the first approved proximal complement inhibitor, can therefore be considered as a relevant therapeutic option in the current management of PNH.