NEJM Evid. 2026 Aug;5(8):EVIDoa2500333. doi: 10.1056/EVIDoa2500333. Epub 2026 Jul 28.
ABSTRACT
BACKGROUND: Eltrombopag is an effective second-line therapy for immune thrombocytopenia (ITP), but its long-term efficacy is limited. All-trans retinoic acid (ATRA) has immunomodulatory effects targeting ITP pathophysiology. We investigated whether combining ATRA with eltrombopag improves long-term outcomes for glucocorticoid-resistant or relapsed ITP.
METHODS: We conducted a multicenter, randomized, open-label trial in adults with glucocorticoid-resistant or relapsed ITP (platelets <30×109/l). Patients were randomly assigned 1:1 to ATRA (12 weeks) plus eltrombopag or eltrombopag monotherapy. The primary outcome was an 18-month sustained response (platelet count ≥30×109/l without clinically significant bleeding or rescue therapy).
RESULTS: Ninety-six patients were randomly assigned, 48 per group. At 18 months, 60% (29/48) in the ATRA-plus-eltrombopag group achieved a sustained response, versus 35% (17/48) in the monotherapy group (odds ratio: 2.78; 95% confidence interval [CI]: 1.22-6.37; P=0.014). The combination was associated with a higher complete response rate (79% vs. 58%; 95% CI for difference, 2 to 39 percentage points) and longer median response duration (75 vs. 37 weeks; hazard ratio for relapse, 0.45; 95% CI, 0.23-0.86). Adverse events were comparable between groups, with no grade 3-4 events or treatment-related deaths. However, clinically significant bleeding of World Health Organization grades 2 or 3 was 21% in the combination group at baseline compared with 10% in the monotherapy group.
CONCLUSIONS: In patients with glucocorticoid-resistant or relapsed ITP, a 12-week ATRA course with eltrombopag significantly enhanced the 18-month sustained response rate compared to eltrombopag alone. (Funded by Capital Health Research and Development of Special Fund and others; ClinicalTrials.gov number, NCT05438875.).
PMID:42517709 | DOI:10.1056/EVIDoa2500333