Vnitr Lek 2025, 71(3):E1-E6 | DOI: 10.36290/vnl.2025.035

Treatment of paroxysmal nocturnal hemoglobinuria patients with complement inhibitors

Jaroslav Čermák, Marie Lauermannová, Jacqueline Maaloufová Soukupová

Ústav hematologie a krevní transfuze, Praha

Introduction: Paroxysmal nocturnal hemoglobinuria represents a rare but serious disorder of hematopoiesis. A deficiency in natural complement inhibitors results in intravascular hemolysis, hemoglobinuria, thrombotic complications and bone marrow failure. Introduction of complement inhibitors in the treatment of PNH completely changed the prognosis of the patients. Our study summarizes experience with the treatment of PNH patients using complement inhibitors in Institute of Hematology in Prague. Patients and treatment: Twenty-one patients with hemolytic PNH were treated with C5 complement inhibitors eculizumab or ravulizumab. Indication criteria were recurrent hemolysis with Hb < 100 g/l +/- transfusion dependency, thrombotic complications or chronic kidney disease. Criteria of treatment response were: increase in Hb level, decrease of number of RBC transfusions or transfusion independence and decrease of RTC count and LDH level. Patients with insufficient response to C5 inhibitors were switched to treatment with C3 inhibitor pegcetacoplan.

Results: Response to the C5 inhibitors was present in 13 out of 21 patients (61,6%), 8 patients did not achieve sufficient response to the treatment, 2 of them developed myelodysplastic syndrome (MDS). Six patients not responding to C5 inhibitors were switched to C3 inhibitor, the treatment response was present in all of them. Taken together, 85,1% of patients responded to complement inhibitor treatment. No thrombotic complications were observed during the treatment, Breakthrough hemolysis occurred in 6 patients (19%). Median survival of treated patients is currently 80,5 months (6,6 years), estimated 10 years and 15 years survival are 100% and 79% respectively.

Conclusions: Treatment with complement inhibitors substantially improved prognosis of PNH patients and our results show (similarly as other studies) that currently almost all treated patients may survive 10 years or more.

Keywords: complement, inhibitor, paroxysmal nocturnal hemoglobinuria, treatment.

Accepted: April 28, 2025; Published: May 16, 2025  Show citation