Long-Term Follow-up of Patients with Aplastic Anemia Enrolled in Phase 2/3 Trials of Immunosuppressive Therapy Plus Romiplostim As a First-Line Treatment: Two-Year Interim Analysis

Background Phase 2/3 clinical trials evaluating the safety and efficacy of immunosuppressive therapy (IST) plus romiplostim in IST-naïve patients with aplastic anemia (AA) have been previously reported (531-003 trial [rabbit ATG+CsA+romiplostim; NCT03957694] and 531-004 trial [CsA＋romiplostim; NCT04095936]). The long-term data on efficacy outcomes and safety profiles are lacking after completion of 27 or 53 weeks romiplostim treatment. As the collection of data on long-term treatment outcomes and disease monitoring is essential owing to the chronic life-threatening nature of the disease, we conducted a prospective observational trial (531-005 [NCT04870346]). Aim This study aimed to evaluate the long-term efficacy and safety of romiplostim after completion of treatment among IST-naïve patients with AA registered in the 531-003 and 004 trials who were planned to be followed for up to 5 years. This report presents the results of the 2-year interim analysis. Methods Patients who had participated in the 531-003 and 004 trials and gave written informed consent to participate in this study were registered. To date, data were collected at least once every 6 months. The study period was from December 2019, and it will continue through 30 June 2025. The primary endpoint was the hematological response (overall response rate [ORR]) at 2 years and up to 5 years after IST plus romiplostim treatment in the 531-003 and 004 trials. Result Thirty-six patients were enrolled (15 patients from 531-003 and 21 from 531-004). The ORR at 2 years in the whole cohort was 78.8%; 2-year ORRs for patients from the 531-003 and 531-004 trials were 93.3% and 66.7%, respectively. The ORR at 2 years was significantly increased compared with that at 27 weeks. (531-003: 76.5% and 531-004: 41.7%). Hematological parameters, such as platelet count, Hb concentration, neutrophil count, and reticulocyte count, remained stable after 27 weeks. Four patients who had been initially unresponsive before 27 weeks showed a response to continuous romiplostim treatment after 27 weeks, suggesting the presence of late responders. From 27 weeks up to 2 years, no cases of clonal evolution or chromosomal abnormalities were observed. The overall survival at 2 years was 91.6% in the whole cohort. Summary/Conclusion Two phase 2/3 clinical trials that evaluated the efficacy and safety of romiplostim in IST- naïve patients with AA have demonstrated the durable efficacy and tolerability of romiplostim treatment for up to 2 years after the IST＋romiplostim trials (531-003 and 004). We identified “late responders” who were initially unresponsive but then responded to continued administration of romiplostim after 27 weeks. Additionally, some AA patients who had complete/partial response (CR/PR) at 27 weeks were able to sustain CR/PR after discontinuation of romiplostim. This ongoing observational study will continue to follow up patients for up to 5 years.