Combination of Thrombopoietin Receptor Agonists and Rituximab in Relapsed/Refractory Immune Thrombocytopenia: A...

The management of relapsed/refractory immune thrombocytopenia (ITP) remains challenging, and real-world evidence on the combination of thrombopoietin receptor agonists (TPO-RAs) and rituximab is limited.

To evaluate the efficacy, safety, and predictors of response to this combination regimen in a large multicenter cohort.

This retrospective study included 161 patients with relapsed/refractory ITP from six Chinese centers who received TPO-RAs combined with rituximab. Treatment response, durability, safety, and predictors of treatment-free remission (TFR) were analyzed.

Patients were heavily pretreated, with a median of four prior therapies and 93% refractory to previous treatment. The best overall response rate was 83%, with 43% achieving complete response and 40% partial response. After a median follow-up of 22 months, 30% of patients attained TFR. Notably, rituximab restored platelet response in 29% of patients primarily refractory to their prior TPO-RA and in 40% of those with secondary resistance. Multivariate analysis identified female sex, age <45 years, disease duration <24 months (OR 10.70), and positive antinuclear antibody (OR 4.36) as independent predictors of TFR, while prior TPO-RA exposure (OR 0.24) and low-dose rituximab (OR 0.33) were associated with lower TFR odds. Adverse events occurred in 16% of patients and were mostly mild to moderate, with no treatment-related deaths.

Combination therapy with TPO-RAs and rituximab is effective and well tolerated in relapsed/refractory ITP, particularly in female patients aged <45 years with disease duration <24 months and in anti-ANA-positive patients. In a subset of patients, the combination restored sensitivity to previously ineffective TPO-RAs.