With an aim to prevent the incidence of graft-versus-host disease (GvHD) in patients, Dipenkumar Modi et al. from Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, conducted a prospective phase II study ( NCT01246206) which is evaluating the safety and efficacy of a GvHD prophylaxis regimen consisting of tacrolimus (calcineurin inhibitor) and thymoglobulin ( in vivoT-cell depletion) combination in patients undergoing matched-related allogeneic hematopoietic stem cell transplantation (AHSCT). The results of the study were reported in a Letterto the Editor of the American Journal of Hematology.
A Simon’s two-stage design was used for this study. In the first stage, 20 patients (median age = 59 years, range: 38–69) in complete or partial remission at the time of transplant were included in this study. Patients were administered intravenous rabbit thymoglobulin (0.5 mg/kg on day 3, 1.5 mg/kg on day 2 and 2.5 mg/kg on day 1) prior to transplant and tacrolimus 0.03 mg/kg starting on day -3 to day 60. The primary objectives of the study were the incidence and severity of acute GvHD (aGvHD). The median follow-up was 54.3 months (95% CI, 43.6–NR).
- 1-year cumulative incidence of aGvHD
- Grade II–IV: 45% (95% CI, 22.3–65.4%)
- Grade III–IV: 10% (95% CI, 1.6–27.8%)
- 1-year cumulative incidences of chronic (cGvHD) and extensive GvHD were 50% (95% CI, 26.0–70.0%) and 45% (95% CI, 22–65.5%)
- 1-year relapse rate: 25% (95% CI, 8.7–45.5%)
- Median time to relapse: 317 days (range, 31–994)
- 1-year survival rates
- Overall survival: 85% (95% CI, 10.7–100%)
- Relapse-free survival: 65% (95% CI, 47.1–89.7%)
- GvHD-free relapse-free survival: 30% (95% CI, 15.4–58.6%)
- 1-year non-relapse mortality rate: 10% (95% CI, 1.6–27.8%)
- Causes of death in eight patients were recurrence or progression of underlying malignancies (62.5%), cGvHD (25%) and cardiac failure (12.5%)
In this study, pre-specified threshold for aGvHD was set in nine patients. However, the use of GvHD prophylaxis consisting of tacrolimus and thymoglobulin did not meet the primary endpoint in reduction of grade II–IV aGvHD below the pre-determined threshold as 12 of the 20 patients enrolled in this study developed aGvHD, which led to the termination of this phase II study after the first stage.
Despite this outcome, it was found that severe GvHD was low and a favorable safety profile with comparable relapse rate, survival and NRM was observed with this prophylactic regimen. The researchers concluded that further studies in larger sample size are warranted to better define the role of this regimen in GvHD prevention possibly “using grade III–IV GvHD as an endpoint”.