Efficacy and safety of immunosuppressive therapy combined with eltrombopag for severe aplastic anemia: a systematic review and meta-analysis

Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.

We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.

A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58–2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60–2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75–1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83–4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08–3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85–2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15–2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93–2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46–1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.

EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.