Gvhd Prophylaxis with ATG and Ptcy Vs Ptcy-Based Regimens in Haploidentical Stem Cell Transplantation: A Cell Therapy Transplant Canada Registry Study

Introduction Allogeneic stem cell transplantation using a related haploidentical donor (haploSCT) is an alternative option for patients without a suitable fully matched donor. Post-transplant cyclophosphamide-based (PTCy) prophylaxis is the most used regimen in Canada to prevent graft-vs-host disease (GVHD) in haploSCT. Although effective at preventing severe forms of acute (aGVHD) and chronic GVHD (cGVHD), efforts remain to optimize this regimen to further decrease risks without increasing non-relapse mortality (NRM) or relapse. The Princess Margaret Cancer Centre (PMCC) transplant program has added anti-thymocyte globulin (ATG)(4.5mg/kg over days -3 to -1) to PTCy (50mg/kg/day on days +3 and +4) as their standard regimen in haploSCT. Thus, we sought to compare haploSCT outcomes between ATG+PTCy and PTCy-based regimens in the Canadian context. Methods We conducted a retrospective study using data from PMCC (ATG+PTCy-based cohort) and the Cell Therapy Transplant Canada (CTTC) registry (PTCy-based cohort). Adult recipients of a haploSCT for a hematologic malignancy in a Canadian centre between 2016-2023 were included. The Kaplan-Meier method was used to estimate OS and GVHD-relapse free survival (GRFS). Cumulative incidence functions were used for relapse, NRM, aGVHD, and cGVHD estimation. Results A total of 385 patients were included, with 148 receiving ATG+PTCy and 237 PTCy. Transplant indications were AML (51%), MDS (18%), ALL (15%), lymphoma (8%), and MPNs (8%). Median age was 58 years and 62% were male. Karnofsky Performance Status (KPS) was >80% in 72% of the patients. Myeloablative conditioning was utilized in 36% of transplants. Primary disease was the most common cause of death in the cohort. ATG+PTCy resulted in less moderate or severe cGVHD as assessed by NIH consensus criteria when compared to PTCy (2-year cumulative incidence (CI) 11% vs 23%; 95%CI 1.2-3.4; p=0.009). There was no difference in grade 2-4 aGVHD (CI 22% vs 30%; 95%CI 0.84-1.83; p=0.29). No difference was found in 2-year OS (56% vs 61%; 95%CI 0.2-1.18; p=0.25), 2-year GRFS (44% vs 45%; 95%CI 0.72-1.08; p=0.24), or 2-year CI of relapse (25% vs 28%; 95%CI 0.76-1.33; p=0.97). 2-year NRM was higher when ATG+PTCy was used as compared to PTCy alone (27% vs 18%; 95%CI 0.42-0.99; p=0.047). Conclusion This study is the largest real-world cohort to compare ATG+PTCy and PTCy-based GVHD prophylaxis regimens in haploSCT recipients. We show that combining ATG+PTCy significantly decreases the incidence of moderate to severe cGVHD without impacting relapse, OS, or GRFS. This possibly translates into improvements in recipients’ quality of life and healthcare utilization. The addition of ATG to PTCy was associated with an increased incidence of NRM. More data are required to optimize a promising prophylactic regimen in this group of patients.

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