(255) Survival Benefit of Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 586

Presenting Author(s)

Ami Patel, PhD
– Alexion Pharmaceuticals, Wilmington, Delaware, United States

Co-Author(s)

Jesse Metzger, PhD
– Parexel International, United States
Louis Terriou, MD
– CHU Lille, Service de Médecine Interne et Immunologie Clinique, France
Christopher Patriquin, MD MSc
– Division of Medical Oncology and Hematology, University Health Network, University of Toronto, Canada
Morag Griffin, MD
– Department of Haematology, Leeds Teaching Hospitals NHS Trust, United Kingdom
Jong Wook Lee, MD PhD
– Department of Hematology, Seoul St. Mary’s Hospital, The Catholic University of Korea, Republic of Korea
Phillippe Gustovic, MD
– Alexion, AstraZeneca Rare Disease, Switzerland
Wei Jiang, MS
– Alexion, AstraZeneca Rare Disease, Boston, MA, United States
Jeff Szer, MBBS
– Department of Clinical Haematology, Peter MacCallum Cancer Centre and the Royal Melbourne Hospital, Australia

Background: Eculizumab has transformed treatment of paroxysmal nocturnal hemoglobinuria (PNH), an ultrarare disease characterized by intravascular hemolysis, by improving survival to that of a general population.

Objectives: This analysis describes the overall survival of an international cohort of eculizumab-treated patients compared with an untreated cohort using data from the International PNH Registry (NCT01374360).

Methods: The study included patients with PNH enrolled in the Registry from March 2007–April 2021. Ever-treated patients received eculizumab for ≥35 days; never-treated patients did not receive eculizumab at any time. Baseline was defined as treatment initiation for ever-treated and registry enrollment for never-treated patients. Cox proportional hazards modeling and Kaplan-Meier estimates were employed. Baseline covariates adjusted for were: presence of high disease activity (HDA) [defined as lactate dehydrogenase ratio ≥1.5 × ULN with ≥1 clinical sign or symptom], age, sex, history of bone marrow failure (BMF), history of thrombotic events, transfusion dependence, and estimated glomerular filtration rate ≤60. Survival time was analyzed using 1) baseline as start time and 2) left-truncation, which analyzes follow-up time from baseline but maps this time from disease start date.

Results: Baseline characteristics of the 1892 ever-treated and 2735 never treated patients were similar for age (44.6 [17.3] vs 46.4 [18.9] years) and sex (53% female). Compared with never-treated patients, more ever-treated patients had HDA (1105/1312 [84.2%] vs 684/2146 [31.9%]) and fewer had history of BMF (822/1010 [45%] vs 1969/2581 [76%]). Among ever-treated patients, those with HDA at baseline experienced the largest reduction in mortality risk (HR [95% CI], 0.46 [0.33–0.64]; n=174). Overall survival probability by treatment status was consistently greater in ever-treated vs. never-treated patients through 20 years of follow-up; survival probability at 20 years was 82% (ever-treated) vs 69% (never-treated) using left truncation. Results were similar without use of left truncation.

Conclusions: Eculizumab treatment improved survival in patients with PNH compared with a never-treated cohort at a comparable time point in their disease course. Covariates were assessed at baseline only and competing risks and time on treatment were not controlled for, which are potential limitations. Though left truncation sought to minimize immortal bias, the bias persisted as some patients began treatment prior to enrollment. Survival benefits conferred by eculizumab treatment were maintained through 2 decades of real-world follow-up.