Impact of eculizumab treatment on paroxysmal nocturnal hemoglobinuria: a treatment versus no‐treatment study

Abstract

Intravascular hemolysis in Paroxysmal nocturnal hemoglobinuria (PNH) can effectively be controlled with eculizumab, a humanized monoclonal antibody that binds complement protein C5. We report here a retrospective comparison study between 123 patients treated with eculizumab in the recent period (>2005) and 191 historical controls (from the French registry). Overall survival (OS) at 6 years was 92% (95%CI, 87 to 98) in the eculizumab cohort versus 80% (95%CI 70 to 91) in historical controls diagnosed after 1985 (HR 0.38 [0.15 to 0.94], P 5 0.037). There were significantly fewer thrombotic events (TEs) in the group of patients treated with eculizumab (4% [1-10]) as compared to the historical cohort (27% [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]). However, we found that TEs may still occur after the initiation of eculizumab treatment and that previous TEs still have a negative impact on survival. Evolutions to myelodysplastic syndrome or acute leukemia were similar in both cohorts. There was less evolution to aplastic anemia in the treatment group. In multivariate analysis, absence of a previous TE and treatment with eculizumab were associated with a better OS. Treatment with eculizumab improves overall survival in classic PNH patients without increasing the risk of clonal evolution.

Atypical presentation of paroxysmal nocturnal hemoglobinuria treated by eculizumab

“…This drug has dramatically changed the natural history of PNH. [7–12] Current evidence indicates that compared with placebo, eculizumab increases transfusion independency and health-related quality of life. Open-label studies and case reports suggest that eculizumab also reduces the risk of further thrombotic events.…”

A mini-review on paroxysmal nocturnal hemoglobinuria and a case of Eculizumab treatment of PNH in elderly MDS patient

“…Despite wide use of anticoagulants in PNH for thrombosis prophylaxis, appropriate risk in the patients remain high, thus enhancing bleeding risks as well [14]. Advent of Eculizumab, a monoclonal antibody which inhibits complement activity, has sufficiently improved results of PNH treatment due to effective control of complement-mediated hemolysis causing thromboses, and improving total survival of the patients [5,17].…”

“…Acute or chronic GvHD was evident in one-third of the patients [4,5]. Meanwhile, Loschi M. et al reported total 6-year survival of 92% among the patients treated by Eculizumab [17]. Hence, HSCT provides a chance for radical PNH treatment.…”

Therapeutic complement inhibition in complement-mediated hemolytic anemias: Past, present and future

“…Indeed, a first report from Kelly et al showed that 5-year overall survival in a cohort of 79 PNH patients on eculizumab was as high as 95% [21], which exceeds that seen in a small cohort of 30 untreated patients [21] or from previous natural history data [22][23][24]. More recently, Loschi et al have conducted a large retrospective comparison between 123 patients receiving eculizumab and 191 historical controls enrolled in their National registry, matched for entry criteria (i.e., hemolytic and/or thromboembolic PNH) [25]. The authors have found that the overall survival of patients on eculizumab was significantly better than that of untreated patients (92% vs 68% at 6 years), possibly due to a lower incidence of thromboembolic events (4% vs 27%).…”