Phase II study of thymoglobulin, cyclosporine and G-CSF for initial treatment of aplastic anemia and low risk myelodysplastic syndrome

Abstract

7093 Background: Aplastic anemia (AA) is commonly treated with equine anti-thymocyte globulin (ATG) and cyclosporine with response rates up to 65%. Thymoglobulin has been used successfully in relapsed/refractory AA, reducing the risk associated with re- administration of equine preparations. Immunosuppressive therapy is also effective in some patients (pts) with myelodysplastic syndrome (MDS). Methods: In this single-arm, phase II study, we investigated efficacy (primary endpoint) and safety (secondary endpoint) of combined thymoglobulin, cyclosporine and G-CSF as a first-line therapy for pts with AA (goal: 30 pts) or low-risk MDS (goal: 30 pts, low or intermediate-1 International Prognostic Scoring System). Thymoglobulin 3.5 mg/kg (or 2.5mg/kg/d for pts ≥55 years) was given for 4 days in the first 10 pts and for 5 days in the remaining pts. Methylprednisone (1 mg/kg/d) was given for 5 days, followed by a tapering dose of oral prednisone. Cyclosporine (5 mg/kg), and G-CSF (5 μg/kg) were also given daily and continued for 6 months or longer. All pts received prophylactic broad-spectrum antibiotics. Responses were assessed approximately 1 to 3 months after therapy. Results: Thirty pts have been enrolled on study; 3 pts chose alternative therapies and 1 pt died before initiation of treatment. Thus 26 (12 with AA and 14 with MDS) have received treatment. Of these, 1 pt was lost to follow-up and 3 have been on study for ≤ 2 months; therefore 10 with AA and 12 with MDS were evaluable. Median age was 65 years (21 - 82) for AA pts and 63 years (47 - 78) for MDS pts. All 10 (100%) AA pts responded (4 CRs, 5 PRs, 1 HI-N). Three of 12 (21%) MDS pts responded (1 CR, 2 PRs). For AA pts median time to response (TTR) was 92 days (30–346) and median response duration was 282 days (14–827). For MDS pts median TTR was 122 days (77–139) and median response duration was 33 days (19–476). Grade 3/4 toxicities were mainly cytopenias and neutropenic fever, occurring in 19 pts (86%). Other grade 3 toxicities included pneumonia, hyperglycemia, elevated ALT and abdominal pain (in 1 patient each). Conclusions: The combination of thymoglobulin, cyclosporine and G-CSF is safe and effective in first-line treatment of AA and has significant activity in low-risk MDS. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genzyme Genzyme