Sirolimus plus roxadustat synergistically enhances immunosuppression and erythropoiesis in pure red cell aplasia: a multicenter trial.

Acquired pure red cell aplasia (aPRCA) is rare and challenging to treat. We investigated the efficacy and safety of sirolimus plus roxadustat in patients with aPRCA (Chinese Clinical Trial Register number, ChiCTR2200065107). We enrolled 82 patients with aPRCA in this prospective single-arm, open-label, multicenter trial between October 2022 and January 2024. Treatment response and safety files were evaluated. The median age was 63 years. Seven patients withdrew during the trial period. Sirolimus plus roxadustat produced an overall response (OR) in 65 patients (90.3%) 3 months after initiation, which included a complete response (CR) in 39 (54.2%) and a partial response in 26 (36.1%). The 3-month CR rate was significantly higher in the newly diagnosed group (65.9% vs. 38.7%; P = 0.022). The 6-month OR rate in the entire cohort was 93.0% (CR, 77.5%; PR, 15.5%). The mean hemoglobin concentration increased from 5.5 ± 1.6 g/dL at baseline to 11.6 ± 2.5 g/dL after 6 months of treatment. The proportions of patients who achieved transfusion independence within 1, 2, and 3 months of treatment were 57.4%, 76.6%, and 89.5%, respectively. The Functional Assessment of Chronic Illness Therapy-Fatigue Scale score and SF-36 survey score significantly improved after treatment. Treatment-related adverse events occurred in 24 patients (29.2%), and four events (4.9%) were grade ≥3. Sirolimus plus roxadustat is a promising treatment for aPRCA and has an acceptable safety profile, which warrants further investigation in a randomized setting.