Frontiers in immunology
Long-term outcomes of eltrombopag plus cyclosporine A in eltrombopag-exposed patients with glucocorticoid-resistant or -dependent primary immune thrombocytopenia: a prospective, multicenter, single-arm, phase II study with extended follow-up
By Yuan Y, Jin J, Lai J and 6 others.
Abstract
Background
Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by thrombocytopenia, and approximately 20-30% of patients are refractory to or dependent on first-line glucocorticoid therapy. Our previous prospective phase II study demonstrated promising short-term efficacy of eltrombopag (ELT) combined with cyclosporine A (CsA); however, the durability of response, long-term safety, and patterns of treatment failure remain incompletely characterized.
Methods
We conducted a long-term follow-up analysis of patients enrolled in a multicenter, single-arm, prospective phase II trial (ChiCTR2000040991). In the original study, adult patients with primary ITP who were resistant to or dependent on glucocorticoids were enrolled between December 2020 and December 2023. All patients had previously received ELT monotherapy without an adequate or durable response; therefore, no ELT-naïve patients were included in this cohort. Patients received ELT (initial dose: 50 mg/day) combined with CsA (3 mg/kg/day, target trough concentration: 150-250 μg/L) for 8 weeks, and responders continued maintenance therapy. The follow-up period for the present analysis was extended until January 1, 2026. Safety and long-term Kaplan-Meier analyses included all 28 patients according to the intention-to-treat (ITT) principle, whereas the 8-week efficacy analysis included the 25 patients who completed 8 weeks of treatment. The three patients who discontinued within the first 8 weeks were included in the Kaplan-Meier analysis and counted as treatment-failure events at the time of discontinuation. The primary endpoints were the overall response rate (ORR) and complete response (CR) rate at 8 weeks, and the long-term sustained remission rate. Secondary endpoints included duration of response and the incidence of adverse events. Univariate logistic regression was performed as an exploratory analysis of associations between baseline variables and treatment failure.