# Comparison of the efficacy of thalidomide combined with low-dose rituximab and low-dose rituximab alone in the treatment of steroid-resistant/refractory adult patients with primary immune thrombocytopenia: an open-label trial

## TL;DR

Combining thalidomide with low-dose rituximab improves treatment outcomes for steroid-resistant immune thrombocytopenia patients compared to rituximab alone.

## Contribution

The study introduces a novel combination therapy (thalidomide + low-dose rituximab) and identifies baseline NK cell levels as a potential biomarker for treatment response.

## Key findings

- The combination therapy group had a significantly higher overall response rate (79.17%) compared to low-dose rituximab alone (55.32%).
- Lower baseline levels of CD16+CD56+CD3− NK cells were associated with better treatment outcomes.
- Combination therapy led to a significant increase in NK cell counts after six months compared to rituximab alone.

## Abstract

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by reduced platelet counts, leading to an increased risk of bleeding and substantial impairment patients’ quality of life. Although rituximab (RTX) is commonly employed as a second-line treatment for patients with steroid-refractory or steroid-resistant ITP, its long-term efficacy as monotherapy remains limited.

This study aimed to evaluate the efficacy and safety of low-dose RTX (LD-RTX) in combination with thalidomide (THD) in the treatment of patients with steroid-refractory or steroid-dependent ITP.

A total of 100 patients with ITP who failed first-line treatment at Shangqiu First People’s Hospital and Funing County People’s Hospital between January 2021 and January 2025 were enrolled in a randomized controlled trial. Participants were assigned to one of two groups: the LD-RTX group (ctrl-group) or the T + LD-RTX group (thal-group).

The overall response rate in the thal-group was significantly higher than in the ctrl-group (79.17% vs. 55.32%; p < 0.05). Among patients who achieved a therapeutic response, baseline levels of CD16+CD56+CD3− natural killer (NK) cells were significantly lower in the complete remission (CR) group (78.81 ± 20.15 cells/μL) and partial remission (PR) group (91.82 ± 28.64 cells/μL) compared to the non-remission (NR) group (139.00 ± 42.42 cells/μL; p < 0.05). In the thal-group, the absolute count of CD16+ NK cells in responders (CR + PR) increased from 84.63 ± 24.85 cells/μL at baseline to 138.71 ± 19.20 cells/μL after 6 months. In contrast, in the ctrl-group, NK cell counts increased slightly from 92.96 ± 23.17 cells/μL to 129.73 ± 28.50 cells/μL over the same period. Patients with lower pre-treatment levels of CD16+CD56+CD3− NK cells demonstrated better therapeutic responses, and a significant post-treatment increase in NK cell counts was observed in the combination group (p < 0.05). ROC analysis identified a threshold of 110.5 cells/μL for the absolute NK cell count (sensitivity: 81.6%; specificity: 100.0%) and 5.72% for the NK cell percentage (sensitivity: 65.8%; specificity: 100.0%) as predictive markers for achieving CR or PR. Lower baseline values were associated with more favorable outcomes.

The combination of THD LD-RTX represents a promising therapeutic strategy for patients with steroid-refractory or steroid-dependent ITP. Furthermore, baseline NK cell levels may serve as a useful biomarker for predicting treatment response.