All-Trans Retinoic Acid plus Eltrombopag for Refractory/Relapsed Immune Thrombocytopenia.

Authors

Haixia Fu, Zhuoyu An, Menglin Li, Yi Liu, Hui Liu, Ru Feng, Zhao Wang, Gaochao Zhang, Jingwen Wang, Lei Yang, Qiusha Huang, Peng Zhao, Mengtong Zang, Chencong Wang, Yun He, Xiaolu Zhu, Huixin Liu, Yu Wang, Lanping Xu, Yuan Kong, Yingjun Chang, Xiangyu Zhao, Yang Wang, Guoshuang Feng, Xiaojun Huang, Xiaohui Zhang

Published in

NEJM evidence. Volume 5. Issue 8. Pages EVIDoa2500333. Epub Jul 28, 2026.

Abstract

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.
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).
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.
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
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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