Efficacy and safety of TPO-RA combined with sirolimus in the treatment of relapsed immune thrombocytopenia.

BACKGROUND

Relapsed immune thrombocytopenia (ITP) poses challenges in treatment. Thrombopoietin receptor agonists (TPO-RAs) are recommended as second-line therapy, but the efficacy of monotherapy is limited to about 60%. Our preliminary studies suggest sirolimus is effective for relapsed ITP. This study aimed to evaluate the efficacy and safety of TPO-RA combined with sirolimus in treating relapsed ITP.

METHODS

A retrospective analysis was conducted on 50 patients with relapsed ITP, all of whom received TPO-RAs (hetrombopag and eltrombopag) combined with sirolimus therapy. The primary endpoints were the overall response rate (ORR) at 4, 8, and 12 weeks of treatment. Secondary endpoints included safety of this regimen and subgroup analysis.

RESULTS

ORR at 4, 8, and 12 weeks was 61%, 76%, and 82%, respectively, with a median time to response of 7 days. Mean platelet counts at 2-, 4-, 8-, and 12-weeks post-treatment were 71 ± 12.7 × 109/L, 86 ± 10.9 × 109/L, 128 ± 19.7 × 109/L and 131 ± 17.2 × 109/L, respectively. Whether it is hetrombopag or eltrombopag, when combined with sirolimus, there is no statistically significant difference in efficacy between the two subgroups. TPORAs combined with sirolimus as second-line treatment and as third-line or beyond treatment showed no difference in efficacy. Among ANA-positive patients, the ORR shows no significant difference compared to the ANA-negative group (p > 0.05). Patients with ITP for less than one year are more likely to benefit from this treatment regimen (p = 0.003).

CONCLUSIONS

The combination of TPO-RAs and sirolimus significantly improved platelet counts and sustained response rates. The regimen demonstrated a manageable safety profile, offering a novel therapeutic option for relapsed ITP.