Background: Thrombopoietin receptor agonists combined with ALG/ATG and cyclosporine are the standard immunosuppressive therapy for severe aplastic anemia (SAA). However, early response rates remain suboptimal. Cyclophosphamide has shown efficacy in relapsed/ refractory AA. Therefore, we designed a clinical trial to evaluate cyclophosphamide combined with the standard immunosuppressive therapy as a first-line treatment for SAA and very severe aplastic anemia (VSAA) to improve early response rates.

Methods: This study was a single-arm, prospective, phase II clinical trial using a Simon two-stage design. The primary endpoint was the overall response rate (ORR) at 3 months. Newly diagnosed SAA/VSAA patients received a combination treatment as follows: porcine ALG at 25 mg/kg/day from days 1 to 5, cyclosporine at 3-5 mg/kg/day continuously, herombopag at 15 mg/day starting from day 1 and continued for 6 months, cyclophosphamide at 20 mg/kg/day on days 29-30 and days 43-44.

Results: Among the 36 patients evaluable for the primary endpoint, the 3-month ORR was 66.7% (24/36), with a complete response (CR) rate of 8.3% (3/36) and a superior remission rate of 22.2% (8/36). 28 patients were evaluable for the 6-month efficacy, the ORR at 6 months was 75% (21/28), with a CR rate of 28.6% (8/28) and a superior remission rate of 64.3% (18/28). The most common adverse events after cyclophosphamide were grade 1-2 gastrointestinal reactions (100%) and grade 3-4 neutropenia (66.7%), with a median duration of 6 days (range: 4-33 days). The infection rate within 3 months was 58.3% (21/36). The mortality rate within 3 months was 0%.

Conclusion: Cyclophosphamide in combination with standard immunosuppressive therapy as first-line treatment shows good safety and efficacy, with two-thirds of patients achieving a response and becoming transfusion-independent within 3 months.

Disclosures

No relevant conflicts of interest to declare.

This content is only available as a PDF.
2024
Sign in via your Institution