PB0722 - Resolution of Hemolysis in a patient with PNH treated with Pegcetacoplan

Background: Paroxysmal nocturnal hemoglobinuria(PNH) is a rare hematopoietic stem cell disorder that presents with hemolytic anemia, thrombosis, and cytopenias. Complement inhibition with C5 inhibitors like eculizumab can be highly effective in treating intravascular hemolysis from PNH. However, approximately 50% of patients on C5 inhibitors have continued symptoms due to extravascular hemolysis.

Aims: Pegcetacoplan, a C3 inhibitor, is capable of blocking both intravascular and extravascular hemolysis. This case illustrates a patient with suboptimal response to eculizumab who had markedly decreased hemolysis after starting pegcetacoplan.

Methods: A 29-year-old woman with no significant past medical history presented to the clinic with a one month history of fatigue and dyspnea. Physical examination was remarkable for pallor and scleral icterus. Initial labs showed a hemoglobin of 4.2 g/dL and a platelet count of 16 x 10^9/L. She was admitted to the hospital for platelet and red blood cell transfusions. Additional labaratory studies revealed an LDH of 461 IU/L and a haptoglobin of 8 mg/dL, consistent with hemolysis. Bone marrow biopsy revealed a cellularity of 20%, PIGA mutation returned positive, and flow cytometry revealed a PNH clone in 90% of neutrophils and monocytes. Studies were consistent with an aplastic anemia in the setting of PNH.

Results: She began eculizumab therapy and had continued hemolysis, requiring biweekly red blood cell transfusions and intermittent platelet transfusions. Repeat bone marrow biopsy revealed 60% cellularity, and flow cytometry showed a PNH clone in 99% of monocytes and neutrophils and in 20% of red blood cells, consistent with an increase in size of the previously diagnosed PNH clones. She was then transitioned to pegcetacoplan, with resolution of her hemolysis. She is no longer requiring transfusion support, and serum LDH and haptoglobin are now within normal limits.

Conclusion(s): This case highlights the importance of considering pegcetacoplan in patients with PNH with continued hemolysis on a C5 inhibitor.