A randomized pilot trial comparing anti-thymocyte globulin with anti-thymocyte globulin plus post transplant cyclophosphamide for prophylaxis against acute and chronic graft versus host disease in matched donor hematopoietic cell transplants – a study from the Cell Therapy Transplant Canada/ Australasian Leukemia Lymphoma Group Consortium

In a randomized pilot trial we compared ATG (standard Arm A, 4.5 mg/kg) with ATG plus PTCy (experimental Arm BE, ATG 4.5 mg/kg, PTCy 100 mg/kg). The primary safety endpoint was overall survival at 100 days. We analyzed 79 patients with AML (n = 55) or MDS (n = 24). Median age (range) was 59 (19 to 74), 47 (59.5%) were male. Conditioning was either myeloablative (n = 49) or reduced intensity (n = 30). Donors were 8/8 HLA-matched. Overall survival at 100 days was 95.0% (37 of 39 patients) vs 94.9% (38 of 40 patients) in arm A vs arm BE (p > 0.9). In arms A versus BE, serious adverse events (SAEs) occurred in 26 (65.0%) and 25 (64.1%) patients, graft failure occurred in 3 and 1 patients (p > 0.9), median (range) days to neutrophil engraftment were 19 (10–45) versus 22 (15–56) days p = 0.007), cytomegalovirus and Epstein-Barr virus reactivations occurred in 11 and 7 patients (p = 0.45) and in 6 and 5 patients (p = 0.29). Overall survival at 12 months was 72.5% versus 75.8% (p = 0.79), cumulative incidence at 6 months of relapse was 15.0% versus 15.7% (p = 0.88) and of non-relapse mortality (NRM) 7.5% versus 8.0 (p = 0.45). The combination of ATG and PTCy can safely be used in phase III trials.Registration: clinicaltrials.gov (NCT04202835), November 29, 2019.