Durable response to iptacopan therapy in a patient with classic paroxysmal nocturnal hemoglobinuria and C3-mediated extravascular hemolysis during eculizumab treatment: a clinical case

Serdyuk O.D., Starikova E.V.

1) Clinical Oncology Dispensary No. 1, Krasnodar, Russia; 2) Clinical Oncology Dispensary No. 2, Sochi, Russia

Background: Classic paroxysmal nocturnal hemoglobinuria (PNH) is characterized by predominant complement-mediated hemolysis, anemia, hemoglobinuria, and associated clinical complications, in the absence of significant bone marrow failure. While C5 inhibitors control intravascular hemolysis, some patients continue to experience clinically significant anemia caused by C3-mediated opsonization of erythrocytes and their subsequent extravascular destruction. In such cases, normal or near-normal lactate dehydrogenase (LDH) levels do not rule out ongoing hemolytic activity.
Description of the clinical case: The case of a female patient (born in 2001) with classic PNH is reported. The disease onset in 2020 was marked by an episode of dark urine, severe anemia, transfusion dependence, and significantly elevated LDH levels. The diagnosis was confirmed via high-precision flow cytometry; bone marrow analysis revealed no diagnostic signs of aplastic anemia or myelodysplastic syndrome. The patient had been receiving eculizumab since October 2021. While receiving anti-C5 therapy, control of intravascular hemolysis was achieved (as evidenced by LDH levels); however, anemia, reticulocytosis, indirect hyperbilirubinemia, a positive direct antiglobulin test (C3d+++), and transfusion dependence persisted. Iptacopan therapy was initiated in October 2024. By week 4, hemoglobin levels rose from 88 g/L to 120 g/L, total bilirubin decreased from 37.1 µmol/L to 8.3 µmol/L, and the absolute reticulocyte count dropped from 197×10⁹/L to 34.2×10⁹/L. At week 78 of follow-up, the clinical and laboratory response was maintained: hemoglobin was 121 g/L, reticulocytes were 93×10⁹/L, total bilirubin was 10.8 µmol/L, and LDH was 35 U/L. No episodes of breakthrough hemolysis, adverse events, or need for blood transfusions following the initiation of iptacopan therapy were recorded.
Conclusion: This case report demonstrates a sustained clinical and laboratory response to iptacopan therapy in a patient with classic PNH who had shown a suboptimal response to prior eculizumab therapy associated with C3d-mediated extravascular hemolysis. This case highlights the need for a comprehensive assessment of the response to anti-C5 therapy, incorporating not only LDH levels but also hemoglobin, absolute reticulocyte count, bilirubin (including fractions), transfusion requirements, and the direct antiglobulin test with C3d detection.

For citations: Serdyuk O.D., Starikova E.V. Durable response to iptacopan therapy in a patient with classic paroxysmal nocturnal hemoglobinuria and C3-mediated extravascular hemolysis during eculizumab treatment: a clinical case. Pharmateca. 2026;33(6):83-88. (In Russ.). DOI: https://dx.doi.org/10.18565/pharmateca.2026.6.83-88

Authors’ contribution: Both authors participated in patient monitoring, clinical data collection, and the preparation of the final manuscript. Both authors approved the final version of the article and are responsible for the accuracy of the data presented.
Conflicts of interest: The authors confirm that they have no conflicts of interest to declare.
Funding: The study was conducted without any sponsorship.

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About the Authors

Olga D. Serdyuk, Clinical Oncology Dispensary No. 1, Krasnodar, Russia; 7-18@mail.ru (corresponding author)
E.V. Starikova, Clinical Oncology Dispensary No. 2, Sochi, Russia