Optimizing Care in Patients with Paroxysmal Nocturnal Hemoglobinuria: Managing Suboptimal Response and Uncontrolled Disease

Marc Bienz,1 Monika Oliver,2 Catherine Sperlich,3 Christopher J Patriquin4 1Division of Hematology, Jewish General Hospital, Montreal, QC, Canada; 2Division of Hematology, University of Alberta Hospital, Edmonton, AB, Canada; 3Division of hematology and oncology, CISSS- Montérégie-Centre/Hôpital Charles-Le Moyne, Greenfield Park, QC, Canada; 4Division of Medical Oncology and Hematology, Toronto General Hospital/University Health Network, Toronto, ON, CanadaCorrespondence: Christopher J Patriquin, Toronto General Hospital/University Health Network, 200 Elizabeth Street, Toronto, ON, M5G2C4, Canada, Tel + 1-416-340-5233, Email Christopher.patriquin@uhn.caAbstract: The treatment of patients with PNH has been revolutionized by terminal complement C5 inhibitors, which control intravascular hemolysis and thrombosis, reduce morbidity and mortality, and improve life expectancy to that approaching people without PNH. In recent years, approval of proximal inhibitors provides clinicians and patients with additional treatment options such that patients who have residual anemia, ongoing symptoms affecting quality of life, or are intolerant to terminal C5 inhibition now have options to optimize treatment. Here, we provide five questions to guide clinicians involved in the care of patients with PNH in assessing treatment response on terminal inhibitors and identifying patients who might benefit from therapy adjustments. We also provide insights into additional treatment options.Keywords: proximal complement inhibitor, C5 inhibitor, intravascular hemolysis, extravascular hemolysis, breakthrough hemolysis, treatment response