The combined use of reduced-dose post-transplant cyclophosphamide (PTC-gamma) and low-dose antithymocyte globulin (ATG) substantially reduced the incidence of acute graft vs host disease (GVHD) and improved survival outcomes compared with ATG alone among patients who underwent haploidentical, peripheral blood stem cell transplant (haplo-PBSCT), according to the results of a study published in the British Journal of Haematology.
GVHD prophylaxis for haplo-PBSCT commonly includes either PTC-gamma or ATG. The aim of this trial was to determine if the combination of the regimens at a lower dose could improve efficacy.
The multicenter trial randomly assigned 122 patients to receive reduced-dose PTC-gamma plus low-dose ATG or standard-dose ATG with fludarabine, busulfan, and cytarabine (FBA) conditioning. The primary endpoint was cumulative incidence of grade II-IV acute GVHD. Secondary endpoints included engraftment, cumulative incidences of grade III-IV acute GVHD, chronic GVHD, and survival.
All patients in both treatment arms achieved 30-day neutrophil recovery, with a similar time to engraftment. All patients also achieved sustained myeloid engraftment. The rate of platelet engraftment, with a 60-day recovery of 91.8% in the PTC-gamma/ATG group and 93.4% in the ATG group (P =.164); however, the recovery was more rapid in the combined group with a median of 13.5 days compared with 21 days in the ATG only group (P =.003).
The 100-day cumulative incidence of acute GVHD was lower in the combination group. There were 11.5% of patients in the PTC-gamma/ATG group who developed grade II-IV acute GVHD compared with 39.3% of patients in the standard ATG group (hazard ratio [HR], 0.29; 95% CI, 0.13-0.64; P =.001). The rate of grade III-IV acute GVHD at day 100 was also significantly lower with PTC-gamma/ATG at 6.6% compared with 24.6% with ATG alone (HR, 0.30; 95% CI, 0.11-0.82; P =.014).
The 2-year cumulative incidence of chronic GVHD was similar regardless of prophylaxis regimen at 24.2% and 39.9% in the PTC-gamma/ATG and ATG-only arms, respectively (HR, 0.56; 95% CI, 0.28-1.11; P =.099).
Survival outcomes were also improved with the combination of PTCγ and ATG. The 2-year overall survival was 75.4% with the combination compared with 54.1% with ATG alone (HR, 0.47; 95% CI, 0.24-0.91; P =.021). Disease-free survival was similarly improved with PTC-gamma/ATG at 72.7% compared with 55.0% with ATG alone (HR, 0.53; 95% CI, 0.28-0.99; P =.0444). The GVHD-free/relapse-free survival was 61.3% in the PTC-gamma/ATG group compared with 42.3% in the ATG group (HR, 0.54; 95% CI, 0.32-0.92; P =.022).
The authors concluded that “our results demonstrate that the addition of low-dose ATG to reduced-dose [PTC-gamma] with FBA conditioning is a promising strategy in haplo-PBSCT.”
Zhang W, Gui R, Zu Y, et al. Reduced-dose post-transplant cyclophosphamide plus low-dose post-transplant anti-thymocyte globulin as graft-versus-host disease prophylaxis with fludarabine–busulfan–cytarabine conditioning in haploidentical peripheral blood stem cell transplantation: A multicentre, randomized controlled clinical trial. Br J Haematol. Published online October 6, 2022. doi: 10.1111/bjh.18483