Safety and efficacy of eltrombopag in splenectomized and nonsplenectomized patients with immune thrombocytopenia: Results from the extend study

Background:Although splenectomy remains an appropriate treatment for ITP, it is associated with adverse events (AEs). The most recent guidelines for ITP indicate that splenectomy should be designated a second-line treatment and delayed for 6-12 months. Eltrombopag is an oral thrombopoietin receptor agonist (TPO-RA) approved in Europe for treatment of splenectomized adult chronic ITP patients who are refractory to other treatments, and as a second-line treatment for adult nonsplenectomized patients in whom surgery is contraindicated. The EXTEND study assessed long-term safety and efficacy of eltrombopag in ITP patients previously enrolled in 6-week or 6-month placebo-controlled trials. Aims: To compare the safety and efficacy of long-term eltrombopag treatment in patients with or without splenectomy in the EXTEND trial. Methods: Eltrombopag was started at 50 mg weekly and titrated to maintain platelet counts 50-200 Gi/L. Results: Among patients enrolled in EXTEND (N=302), 115 splenectomized (38%) and 187 nonsplenectomized (62%) patients had similar characteristics at baseline, except that more splenectomized patients were receiving ITP medications at baseline (47% vs 25%) and more had a history of bleeding (23% vs 13%). Greater than half of both groups received eltrombopag for ≥24 months. After eltrombopag treatment, a greater proportion of nonsplenectomized patients achieved platelets ≥50 Gi/L than splenectomized ones, and was consistent by age group (Table). Nonsplenectomized patients experienced proportionately fewer serious bleeding AEs (Table). Rates of any bleeding AE were experienced by 49 (26%) and 35 (30%) nonsplenectomized and splenectomized groups, respectively. Events occurring in ≥4% of patients in the splenectomized and nonsplenectomized groups, respectively, included mouth hemorrhage (4% and 1%), epistaxis (14% and 6%), petechiae (8% and 2%), ecchymosis (2% and 4%), contusion (3% and 4%), and hematuria (2% and 4%). In each group, 13% had a sustained reduction or permanently stopped at least one concomitant ITP medication without having received any on-treatment rescue medication. Splenectomized patients had higher rates of Grade 1-4 World Health Organization bleeding at baseline (64% vs 52%), but rates declined in both groups over time. Summary/Conclusions: Long-term treatment with eltrombopag increased platelets in both nonsplenectomized and splenectomized patients, with numerically higher response rates in the former. Rates of AEs were similar to those in patients with splenectomy. (Table Presented).