Background
Multicenter, randomized, open-label trial (N=96; China). Adults with glucocorticoid-resistant or relapsed immune thrombocytopenia (platelets <30x10^9/L). Rationale: eltrombopag's long-term durability is limited; all-trans retinoic acid (ATRA) has immunomodulatory effects targeting ITP pathophysiology.
Results
Interventions and follow up: Arm A: ATRA PO x12 wk + eltrombopag
Arm B: Eltrombopag monotherapy
Primary endpoint: 18-month sustained response (platelets ≥30x10^9/L without clinically significant bleeding or rescue therapy)
mFollow up: 18 mo (fixed assessment)
Results: Sustained response at 18 mo: 60% vs 35% (OR 2.78; 95% CI 1.22-6.37; P=.014)
Complete response: 79% vs 58% (95% CI for difference 2-39 percentage points)
Median response duration: 75 vs 37 wk (HR for relapse 0.45; 95% CI 0.23-0.86)
Arm B: Eltrombopag monotherapy
Primary endpoint: 18-month sustained response (platelets ≥30x10^9/L without clinically significant bleeding or rescue therapy)
mFollow up: 18 mo (fixed assessment)
Results: Sustained response at 18 mo: 60% vs 35% (OR 2.78; 95% CI 1.22-6.37; P=.014)
Complete response: 79% vs 58% (95% CI for difference 2-39 percentage points)
Median response duration: 75 vs 37 wk (HR for relapse 0.45; 95% CI 0.23-0.86)
Adverse events
Grade 3-4: none in either arm; no treatment-related deaths
Overall: comparable between arms
WHO grade 2-3 bleeding at baseline: 21% (combination) vs 10% (monotherapy) baseline imbalance
Overall: comparable between arms
WHO grade 2-3 bleeding at baseline: 21% (combination) vs 10% (monotherapy) baseline imbalance
Conclusions
A 12-week course of ATRA added to eltrombopag nearly doubled 18-month sustained responses in steroid-resistant/relapsed ITP, with longer response duration and no added toxicity. An inexpensive, widely available repurposed drug makes this an attractive combination strategy for refractory ITP.
Key Limitations
Open-label design with bleeding/rescue-dependent endpoint components; modest size (N=96) and single-country (China) enrollment limiting external validity; baseline WHO grade 2-3 bleeding imbalance between arms (21% vs 10%); eltrombopag dose-response may differ in non-East-Asian populations.
Clinical Context
TPO receptor agonists are guideline-endorsed second-line ITP therapy (ASH 2019), but durable responses remain limited. ATRA joins other eltrombopag add-on strategies under study (diacerein, rhTPO, ianalumab); not yet guideline-incorporated and confirmatory multiregional data are needed before practice change.