Study Examines Relapse Risk in GVHD After Allo-HCT Using 2 Therapy Options

Despite the increase in relapse risk, 2-year survival for patients with graft-versus-host disease (GVHD) who received matched sibling donor (MSD) allogeneic hematopoietic cell transplant (allo-HCT) administered post-transplant cyclophosphamide remained similar compared with patients receiving cyclosporine A with methotrexate prophylactically.

The use of post-transplant cyclophosphamide appears to increase the risk of relapse without affecting graft-versus-host disease (GVHD) risk in patients with acute myeloid leukemia (AML) who undergo matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT), according to a new study.

The report complicates the question of how best to prevent GVHD, since it raises questions about the impact of an increasingly common prophylaxis regimen. The report was published in the journal Transplantation and Cellular Therapy.

Allo-HCT from human leukocyte antigen (HLA)-matched siblings is the “ideal” choice for patients with AML, according to corresponding author Bhagirathbhai Dholaria, MBBS, of the Vanderbilt University Medical Center, and colleagues. Still, 30% to 40% of patients who receive MSD allo-HCT end up experiencing acute GVHD, which in turn is a major cause of mortality and morbidity, Dholaria and colleagues wrote.

The prophylactic combination of cyclosporine A with methotrexate (CSA/MTX) can reduce the risk of GVHD, compared with either drug alone. However, other prophylactic options are available, including the use of post-transplant cyclophosphamide (PTCy), which was first used in bone-marrow grafts and non-myeloablative allo-HCT from an HLA haploidentical (haplo) related donor.

“PTCy promotes graft tolerance by facilitating selective proliferation of regulatory T cells (Treg) and reduces the risk of GVHD,” Dholaria and colleagues wrote.

Previous reports have suggested PTCy can achieve similar GVHD-prevention results to other types of prophylaxis, but the investigators said it was not yet known whether such outcomes would be similar in other transplant settings.

Dholaria and colleagues used a data set from the European Society of Blood and Marrow Transplantation in order to compare the outcomes of 118 patients who were treated with PTCy and 1202 who were given CSA/MTX prior to transplantation. All of the patients received MSD allo-HCT for AML.

Investigators used a matched-pair analysis to evaluate outcomes between the 2 groups. They found 41.1% of patients in the PTCy cohort experienced relapse by 2 years, compared to just 21.3% in the CSA/MTX group.

On the other hand, 180-day grade II-IV acute GVHD rates were similar at 25.2% for the PTCy group and 25.4% in the CSA/MTX group. Two-year chronic GVHD rates were also similar, at 42.6% in both groups.

“In this registry-based observational study of MSD allo-HCT in AML, the risk of acute and chronic GVHD after PTCy was comparable to that with CSA/MTX,” the authors wrote. “The results confirmed the significant impact of GVHD prevention strategy on allo-HCT outcomes.”

The investigators noted that while PTCy appeared to be linked with a greater risk of relapse, that did not translate into a statistically significant gap in 2-year overall survival (70.6% in the PTCy group versus 79.7% in the CSA/MTX group). Two-year leukemia-free survival and GVHD-free relapse-free survival were similarly not significantly different.

Dholaria and colleagues said the question of why a higher relapse rate was observed requires more study to fully understand. They said their study is limited by its retrospective nature, and a prospective study with uniform conditioning and immunosuppressive regimens would be helpful to confirm findings.

Reference

Nagler A, Labopin M, Dholaria B, et al. Graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide versus cyclosporine A and methotrexate in matched sibling donor transplantation. Transplant Cell Ther. Published online November 29, 2021. doi:10.1016/j.jtct.2021.11.013