A new study indicates that tacrolimus may be more effective than cyclosporine A in preventing severe acute graft-versus-host disease (GVHD) in patients undergoing haploidentical hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). The research, published in Bone Marrow Transplantation, analyzed data from 2427 patients and found that while both drugs showed similar long-term survival and relapse rates, tacrolimus demonstrated a significant advantage in reducing severe acute GVHD in the haploidentical transplant setting.
The study, conducted by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, examined the impact of calcineurin inhibitor choice on GVHD outcomes in patients with AML in first complete remission who underwent allogeneic HCT. Patients received either tacrolimus (37%) or cyclosporine A (63%) combined with post-transplantation cyclophosphamide and mycophenolate mofetil as GVHD prophylaxis.
Key Findings on Survival and Relapse
The study revealed no significant differences between the cyclosporine A and tacrolimus groups in key outcomes. Two-year leukemia-free survival (LFS) was 60.5% in the cyclosporine A group and 60.3% in the tacrolimus group (P = .92). Overall survival (OS) was also similar, with 66.3% for cyclosporine A and 64.5% for tacrolimus (P = .75). Nonrelapse mortality was comparable at 18.5% and 18.0%, respectively (P = .44), and cumulative incidences of relapse were 21.1% and 21.7% (P = .51).
Tacrolimus's Impact on Severe Acute GVHD
However, the study highlighted a crucial difference in the incidence of severe acute GVHD. In haploidentical HCT, tacrolimus more effectively prevented severe grade 3-4 acute GVHD compared to cyclosporine A (6.6% vs 9.1%; P = .02). Multivariate analysis confirmed that tacrolimus was associated with a lower risk of severe acute GVHD (HR, 0.64; 95% CI, 0.42-0.98; P = .04) in haploidentical transplant recipients. This effect was not observed in patients receiving unrelated donor transplants (HR, 0.49; 95% CI, 0.2-1.21; P = .12).
Overall GVHD Management
Despite the advantage in reducing severe acute GVHD, the study found no significant differences in other GVHD outcomes. The incidence of grade 2-4 acute GVHD was 27.3% in the cyclosporine A group and 25.2% in the tacrolimus group (P = .34), and the occurrence of extensive chronic GVHD was similar (9.9% vs 11.8%; P = .25). Relapse-free survival at 2 years was also comparable (51.3% vs 50.2%; P = .86).
Clinical Implications
The authors concluded that while both tacrolimus and cyclosporine A, when combined with post-transplantation cyclophosphamide and mycophenolate mofetil, are effective in preventing GVHD with favorable survival outcomes for AML patients in first complete remission, tacrolimus may be the preferred combination partner with mycophenolate mofetil for patients undergoing haploidentical HCT. "In haploidentical HCT, tacrolimus seemed to prevent severe acute GVHD more effectively than cyclosporine A without impact on other outcome parameters," they noted.
