Patients Beyond the Optimal Range of rATG-AUC Still Benefit from the Targeted Dosing Strategy in Unmanipulated Haplo-PBSCT.

ABSTRACT

Rabbit antithymocyte globulin (rATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent graft failure and severe graft-versus-host disease (GVHD). We developed a rATG-targeted dosing strategy based on the optimal areas under the concentration-time curve (AUC) of active rATG. This study compared the outcomes of the optimal AUC arm with nonoptimal AUC arm to assess the effect of the rATG-targeted dosing strategy. Eighty patients (median age 32 years) with hematological malignancies who received their first haplo-PBSCT were enrolled successively. With rATG-targeted dosing, the AUC values of 60 patients (75%, optimal AUC arm) fell within the optimal range (100-148.5 UE/mL/day) and 20 fell beyond this range (nonoptimal AUC arm). In the historical control group of 102 haplo-PBSCT patients who received a fixed dose of rATG (10 mg/kg), less patients fell within the optimal range (57.8%, P = .016). Looking at the nonoptimal AUC arms in both groups, lower cumulative incidence of CMV was noted in the targeted dosing group compared with the historical control group(50.0%, 95% CI, 30.8%-72.9% versus 81.4%, 95% CI, 68.6%-91.3%; P = .004). The cumulative incidences of EBV, relapse, overall survival and disease-free survival tended to be superior in the nonoptimal AUC arm in the targeted dosing group compared with the historical control. In the targeted dosing group, the cumulative incidence of cytomegalovirus (CMV) reactivation on day +180 tended to be lower in the optimal AUC arm (30.0%, 95% CI, 20.1%-43.3%) compared with the nonoptimal AUC arm (50.0%, 95% CI, 30.8%-72.9%, P = .199) without statistical difference. There were no significant differences of acute or chronic GVHD, relapse, nonrelapse mortality, overall survival, disease-free survival or lymphocyte reconstitution between the two arms. In conclusion, the rATG-targeted dosing strategy made the exposure of active rATG in more patients with the optimal AUC range. Even patients who fell beyond this range would still benefit from the strategy.