DP057 | EFFICACY AND SAFETY OF AVATROMBOPAG IN THE REAL-WORLD: A MULTI-CENTRE ITALIAN STUDY

Avatrombopag (AVA) is a potent thrombopoietin receptor agonist (TPO-RA) with an efficacy of about 70% in clinical trials. Data from the real world are limited, particularly concerning the time to response, the cumulative rate of complete response and its duration, and the rate of thrombosis. We studied a large retrospective real-world cohort of patients treated at 12 centers in Italy. We collected prior therapies, plt response (partial for >30x10^9/L or complete for >100x10^9/L) at 1 week from treatment start and then fortnightly, as well as adverse events (AEs) according to CTCAE version 5. In this first analysis, we included 97 patients from 7 centers (59% females/41% males) with a mean age of 47 years at ITP diagnosis and of 57 years at AVA start. Median time from diagnosis to AVA was 10 years and patients had received a median of 3 (1-4) therapies including steroids with or without IVIG, rituximab, TPO-RA, fostamatinib. Notably, 16 patients (16%) received AVA as second line, 14 as third line (14%), and the remaining as further treatment line (70%), and 51 patients (51%) had received a prior TPO-RA, 72% with response. Sixty% of patients had a cardiovascular risk factor including cigarette smoke, hypertension, atrial fibrillation, chronic heart failure, obesity, and diabetes. Before AVA, 70% had severe thrombocytopenia (<30x10^9/L) while the others, with higher PLT counts started AVA to taper steroids or concomitant immunosuppressive agents. As shown in figure 1, during a median follow up of 61.8 weeks (IQR 26-97), overall response rate progressively improved, being 75% at week1 (30% PR and 45% CR), 76% at 1 month (20% PR and 56% CR), 84% at 6 months (27% PR and 57% CR), and 89% at 1 year (17% PR and 72% CR). Improvement of platelets versus baseline was statistically significant at all timepoints (p<0.0001). These trends were confirmed by restricting the analysis to the 68 patients with PLT<30x10^9/L at baseline. Notably, patients treated with AVA as second line had a response rate of 100%, 14/16 CR. Investigators reported an AE in 9 patients (9%), including 5 thrombotic episodes (renal vein thrombosis, myocardial infarction, minor stroke, proximal lower limb thrombosis, and a superficial vein thrombosis), and 4 extreme thrombocytosis. Notably, all patients experiencing thrombosis had at least 2 cardiovascular risk factors (Hypertension 2, Diabetes 3, Obesity 2, Hypercholesterolemia, anti-phospholipid antibodies 3, and smoke 1). At the last follow up, 26 patients (26%) interrupted treatment because of excessive thrombocytosis in 8, no response in 6, thrombosis in 2, and sustained remissions off treatment in 2 (no reason reported in the remaining). In conclusion, this large real-world series confirm the rapid efficacy of AVA in a middle-aged cohort of ITP patients, exceeding 70% after only one week of treatment, making it a suitable treatment particularly in the acute and severe ITP setting. Thrombosis remains the most frequent and feared event occurring in 5% of treated-patients with association with cardiovascular risk factors.