A multicenter, randomized, open-label study of dexamethasone versus romiplostim plus dexamethasone as first line treatment in patients with newly diagnosed immune thrombocytopenia: Interim results of rodex study

Abstract

Abstract Background: Corticosteroids remain the standard first-line treatment for immune thrombocytopenia (ITP), yet less than 40% of patients achieve a sustained response off treatment for 6 months (SROT). Enhancing the efficacy of frontline therapy is an unmet need. Prior reports in difficult-to-treat ITP have suggested that combining immunosuppressive agents with thrombopoietin receptor agonists may yield response rates, particularly in less heavily pretreated patients. However, no data are available on SROT outcomes using this approach as first line treatment. We present first interim analysis from RODEX study. Methods: RODEX (ClinicalTrials.gov NCT05723326) is a randomized (1:1), open-label, phase 3 trial comparing dexamethasone (DEX) to dexamethasone plus romiplostim (ROM+DEX) as first line treatment in adults (≥18 years) with newly diagnosed primary ITP and platelet count <30×10⁹/L. Patients received dexamethasone as monotherapy 40mg/day for 4 days up to 3 cycles either a single cycle dexamethasone followed by weekly subcutaneous romiplostim (Rom). Primary endpoint is sustained response off treatment (SROT), defined as platelet count ≥50×10⁹/L without ITP therapy or rescue for 6 months. Secondary endpoints include early response, relapse rate, safety (CTCAE v4.03), and quality of life (EQ-5D, SF-36 v2, FACIT-F). Cost-effectiveness and healthcare resource utilization are also being assessed. Categorical variables were expressed as relative frequencies and quantitative variables as mean or median and range. Comparisons between groups were performed using the Chi-square or Fisher Exact tests. Statistical significance was established as P < 0.05. Results: Between December 2022 and April 2025, 129 patients were screened; 5 failed inclusion criteria. A total of 124 were randomized: 63 to DEX and 61 to ROM+DEX. One patient in ROM+DEX withdrew consent before treatment; two in DEX never started therapy. Thus, 60 patients in ROM+DEX and 61 in DEX were evaluable. At cutoff (June 30, 2025), 9 ROM+DEX and 14 DEX patients had completed follow-up (6 months since stop treatment or 12 months since start treatment), 31 and 17 were ongoing, and 16 and 17 had discontinued, respectively. Discontinuation in ROM+DEX occurred due to investigator decision (n=7), screening failure (n=4), loss to follow-up (n=2), or other reasons (n=3). In DEX arm, loss to follow-up (n=2), investigator decision (n=2), screening failure (n=4), withdrawal of consent (n=3) and others (n=6). The median age was 54 years (range 18–87), with 54.8% female. No significant differences were noted between arms in baseline platelet counts (21.5 vs 17.4×10⁹/L) or bleeding severity. At baseline, WHO bleeding grades were 20.3% vs 8.1% grade 2–3 in ROM+DEX and DEX groups, respectively. Comorbidities were present in 68.3% (ROM+DEX) and 62.3% (DEX), mainly non-thrombotic cardiovascular disease (15.6%) and diabetes (12.3%). An early platelet response (≥50×10⁹/L at 4 weeks) was seen in 72.1% of DEX and 63.3% of ROM+DEX patients (no statistical difference). In patients with response, in DEX arm patients received a mean of 2.4 DEX cycles. In ROM+DEX arm median Rom treatment duration, total dose and maximal dose was 12.8 weeks (range 3-21), 17 (3-449) mcg/kg and 3 (3-10) mcg/kg, respectively. SROT was evaluable in 43 of 44 responders in DEX and 28 of 38 in ROM+DEX, with 1 and 10 patients respectively still under evaluation. Among evaluable responders, 18/43 (40.9%) in DEX and 20/28 (52.6%) in ROM+DEX maintained SROT (p=0.015). In this group, DEX-arm patients received a mean of 2.4 DEX cycles. In ROM+DEX arm median Rom treatment duration, median total dose and maximal dose was 9.9 weeks (range 0-40.7), 17 (3-101)mcg/kg and 3 (3-6) mcg/kg, respectively Although detailed SAE rates are pending, Interim data suggest better tolerance in the ROM+DEX group. Incidence of adverse events (AEs) was 42% in DEX arm and 20% in ROM+DEX arm (p=0.007). Among patients treated with ROM, 16.7% presented AEs related to drug. At data cut off, there was no statistical differences between ROM+DEX and DEX arm with regard to thrombosis, infections, hypertension or bleeding. Conclusion: These interim results suggest that ROM+DEX SROT and reduces treatment failure compared to DEX as monotherapy as first line treatment in newly diagnosed ITP. The combination regimen appears safe and better tolerated, potentially due to early platelet stabilization and reduced corticosteroid exposure. Final results will clarify long-term.