Prospective randomized trial comparing two doses of rabbit anti‐thymocyte globulin in patients with severe aplastic anaemia

Abstract

Summary The treatment of choice for patients with severe aplastic anaemia (SAA) includes immunosuppressive therapy (IST) with anti‐thymocyte globulin (ATG) and ciclosporin A. However, the optimal dose for rabbit ATG has yet to be established. We herein report the first prospective, randomized, multicentre study comparing two doses of rabbit ATG in patients with SAA. Patients with SAA who required initial IST in Japan (n = 89), China (n = 85) and Korea (n = 48) were enrolled between May 2012 and October 2017. A 1:1 block randomization was employed for two doses of rabbit ATG. In total, 222 patients were randomized, with 112 patients receiving 2·5 mg/kg and 110 receiving 3·5 mg/kg of rabbit ATG for 5 days. The primary endpoint was the haematological response at day 180. After 6 months, no significant difference in response rates was observed between the 2·5 and 3·5 mg/kg groups (49% vs. 48%, P = 0·894). Overall survival at 3 years was similar between the two groups [85% (95% confidence interval [CI], 76%−91%) vs. 91% (95% CI, 82%−96%); P = 0·107]. The current study revealed no significant differences in the efficacy and safety between the 2·5 and 3·5 mg/kg doses of rabbit ATG in patients with SAA. Trial registration: UMIN000011134.

Relationship between plasma rabbit anti‐thymocyte globulin concentration and immunosuppressive therapy response in patients with severe aplastic anemia

“…We previously reported results of the prospective, randomized multicenter study comparing two r‐ATG doses in 222 patients with SAA in Japan, China, and Korea. After 6 months, no significant difference in response rates was observed between the 2.5 and 3.5 mg/kg groups 5 . The current post hoc study aimed to expand on previous findings in the Japanese patient cohort.…”

“…The APBMT AAWG‐01 study (UMIN000011134) was a prospective, randomized, multicenter trial, conducted in patients with SAA who required IST in Japan, China, and Korea between May 2012 and October 2017 5 . Key inclusion criteria were acquired AA, newly diagnosed disease (≤180 days from diagnosis), and without specific previous treatment.…”

“…The optimal dose and regimens of r‐ATG are not yet fully understood. Previously, a prospective randomized multicenter study comparing 2.5 and 3.5 mg/kg doses of r‐ATG was conducted in patients with SAA (APBMT AAWG‐01); however, no difference of hematological response rates was observed between the two groups 5 …”

Prospective validation of the provisional entity of refractory cytopenia of childhood, proposed by the World Health Organization

“…In total, 110 patients were treated with IST using a combination of intravenous ATG and oral CyA at a dose of 6 mg/kg/day within the first 180 days of diagnosis. Of 110 patients, all but five received rabbit ATG (Thymoglobulin; Genzyme, Cambridge, MA, USA) at a dose of 2·5 or 3·5 mg/kg/day for 5 days 11 . Five patients were treated with horse ATG (Lymphoglobulin; Genzyme) at a dose of 15 mg/kg/day for 5 days 12 .…”

“…Of 110 patients, all but five received rabbit ATG (Thymoglobulin; Genzyme, Cambridge, MA, USA) at a dose of 2Á5 or 3Á5 mg/kg/day for 5 days. 11 Five patients were treated with horse ATG (Lymphoglobulin; Genzyme) at a dose of 15 mg/kg/day for 5 days. 12 Responses to IST were evaluated according to previously described criteria.…”