PS1118 IDENTIFICATION OF MIRNA SIGNATURES CORRELATING WITH CLINICAL OUTCOMES IN APLASTIC ANAEMIA

Abstract

Background: There are limited data regarding the effectiveness and safety of either eculizumab or immunosuppressive therapy (IST) when used concomitantly in patients with paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA). The International PNH Registry (NCT01374360) is a prospective, multinational, observational study to collect data on the long-term efficacy and safety of eculizumab treatment. Aims: To evaluate the safety and effectiveness of IST in patients with PNH and AA who are treated concomitantly with eculizumab. Methods: Patients enrolled in the PNH Registry on or before January 1, 2018, with known demographics and enrollment date, who (1) ever reported a diagnosis of AA, (2) were ever treated with eculizumab, and (3) were ever treated with IST (defined as cyclosporine and/or anti-thymocyte globulin) were included. Patients were categorized into 3 cohorts: (I) IST before eculizumab, no overlap; (II) IST before eculizumab, with overlap; (III) eculizumab before IST, with overlap (Panel A). For this analysis, baseline was defined as the later of initiation of IST or PNH disease onset, and last follow-up as the last follow-up on IST (cohort I) or concomitant IST and eculizumab (cohorts II and III). Laboratory values were calculated as the most recent value within 6 months of baseline and last follow-up, and change was analyzed using generalized linear mixed models adjusted for baseline and cohort. Numbers of units of packed red blood cells (RBCs) received were summarized as rates with 95% confidence intervals (CIs) between baseline and last follow-up. Results: The analysis included 283 patients (cohort I, n = 88; cohort II, n = 162; cohort III, n = 33), although not all patients had available laboratory test results at baseline. Results of interest for IST by treatment sequence are shown in Panel B. Overall, 54.1% of patients were female and 85.2% were white. Mean (standard deviation) age at baseline was 35.5 (16.43) years in cohort I, 36.7 (18.21) years in cohort II, and 41.3 (17.05) years in cohort III. Adjusted mean platelet and neutrophil counts improved in patients receiving IST before concomitant eculizumab (cohort II) as well as in those receiving eculizumab before IST, with overlap (cohort III; Panel B) as expected with treatment with IST. Adjusted mean reticulocyte counts and hemoglobin levels both showed a clinically meaningful increase after baseline in cohort II; a clinically meaningful decrease in reticulocyte count was also observed after baseline in cohort III (Panel B). Patients receiving eculizumab prior to concomitant IST (cohort III) had a higher rate (95% CI) of RBC transfusions per patient-years during follow-up (7.2 [6.7, 7.8]) than patients receiving IST prior to concomitant eculizumab (cohort II; 2.8 [2.7, 2.9]). Cohort III also had a higher rate (95% CI) of infections per 100 patient-years during follow-up (23.4 [5.8, 93.4]) than cohort I (1.9 [0.5, 7.4]) and cohort II (4.3 [2.8, 6.6]).Summary/Conclusion: The numbers of patients with available data were limited due to the fact that the Registry was not designed to evaluate the effectiveness of IST. Nevertheless, our findings suggest that IST was effective when used concomitantly with eculizumab in this clinical setting, regardless of the sequence for initiation of treatment with IST or eculizumab. Differences in RBC transfusion rates and laboratory parameters observed across cohorts possibly reflect underlying AA.