Optimized Recombinant Human Thrombopoietin(rhTPO) Regimen Versus Eltrombopag for Pre-Treated Patients with Primary Immune Thrombocytopenia: Interim Results from a Prospective, Multicenter, Randomized Trial (TE-ITP study)

Introduction:

Recombinant human thrombopoietin (rhTPO), a full-length and glycosylated TPO that is highly similar to endogenous thrombopoietin, has been approved by the China State Food and Drug Administration as a second-line treatment option for immune thrombocytopenia (ITP) patients. Due to the individualized treatment needs of ITP patients, it is necessary to develop an optimized rhTPO regimen beyond the fixed 300U/kg/day dose to provide a more effective and personalized treatment approach for ITP patients. Here we report the results of an interim analysis of a multicenter, randomized, controlled trial that explored the efficacy and safety of an optimized rhTPO regimen compared to standard eltrombopag in pre-treated adult ITP patients.

Methods:

This multicenter, open-label, randomized controlled trial was conducted in adult patients (aged ≥18 years) with previously treated ITP who had a disease duration of at least 3 months and a platelet count (PLT) less than 30×10⁹/L. Patients were randomly assigned (2:1) to receive an optimized rhTPO regimen (initial dose of 300U/kg or 600U/kg subcutaneously once daily) or conventional eltrombopag therapy (initial dose of 25mg or 50mg orally once daily) for 42-day treatment period, with randomization stratified by baseline PLT (<20×10⁹/L or ≥20-<30×10⁹/L), and then followed up until Day 180. Dose adjustment was made according to individual PLT response, with the maximum dose of rhTPO set at 600 U/kg/day and the maximum dose of eltrombopag set at 75 mg/day. The primary endpoint was time to response (defined as the time from the start of treatment to the first achievement of PLT ≥50×10⁹/L) within the 42-day treatment period. Secondary endpoints included response rates (defined as PLT ≥30×10⁹/L and at least a 2-fold increase from baseline PLT and absence of bleeding), duration of PLTs ≥50×10⁹/L, time to treatment failure, anti-TPO antibodies, and adverse events. Efficacy endpoints were analyzed in the intention-to-treat population. Safety analyses were performed in all patients who received at least one dose of study medications. This trial was registered with ClinicalTrials.gov, number NCT05583838.

Results:

As of October 27, 2023, 70 patients were randomized to the rhTPO group and 35 to the eltrombopag group. The median age was 52 years (IQR 36-59), and the median PLT before treatment was 17×10⁹/L (IQR 10-23). There were no differences in baseline characteristics between the two groups of patients. Within 42-day treatment period, time to response of rhTPO group was significantly shorter than that of eltrombopag group (median 7 days [95% CI 5-7] vs 15 days [95%CI 9-21]; p＜0.001). In the subgroup with baseline PLT 20-<30×10⁹/L, the median response time of rhTPO at an initial dose of 300 U/kg/day was 7 days, which was significantly faster than the 19 days of eltrombopag at an initial dose of 25 mg/day (p<0.001). Similarly, in the subgroup with baseline PLT <20×10⁹/L, the initial dose of rhTPO at 600 U/kg/day also achieved a median response time of 7 days, which was shorter than the 14 days of eltrombopag at an initial dose of 50 mg/day (p<0.001). The response rate was higher in the rhTPO group compared with eltrombopag group: 65.7% vs. 22.9% at week 1, 81.4% vs. 51.4% at week 4, and 85.7% vs. 65.7% at week 6. The duration of PLTs ≥50×10⁹/L was longer in the rhTPO group with a median of 23 days compared with 16 days in the eltrombopag group(p<0.001). Most adverse events observed were mild to moderate, and no new safety signals were found in either group.

Conclusions:

This is the first study comparing the efficacy and safety of an optimized rhTPO regimen with standard eltrombopag treatment in pre-treated ITP patients. This optimized rhTPO regimen demonstrated superior efficacy in rapidly elevating platelet counts to safe levels, maintaining safe platelet levels, and achieving high response rates, providing an effective therapy for ITP, especially in emergent treatment settings.

Disclosures: No relevant conflicts of interest to declare.