Tacrolimus initial steady state level in post-transplant cyclophosphamide-based GvHD prophylaxis regimens

Area of Science:

• Hematology
• Immunology
• Transplantation Medicine

Background:

• Post-transplant cyclophosphamide (PTCy) combined with tacrolimus (TAC) is a safe and effective prophylaxis for graft-versus-host disease (GvHD) after hematopoietic cell transplantation (HCT).
• Optimal serum levels of TAC in this regimen, specifically the tacrolimus at initial steady state (TISS), are not well-defined.
• Determining the ideal TISS is crucial for balancing transplant outcomes and minimizing TAC-associated toxicities.

Purpose of the Study:

• To investigate the association between TISS levels and transplant outcomes in patients receiving PTCy/TAC prophylaxis.
• To test the hypothesis that a TISS <10 ng/mL is associated with improved transplant outcomes and reduced toxicities.
• To evaluate the impact of TISS on overall survival (OS), disease-free survival (DFS), relapse rate (RR), and GvHD.

Main Methods:

• Retrospective analysis of 210 patients undergoing HCT with PTCy/TAC prophylaxis between January 2013 and June 2018.
• Patients received HCT from haploidentical or mismatched donors, with either flat dose (FD) or weight-based dose (WBD) TAC.
• TISS levels were categorized as <10 ng/mL or ≥10 ng/mL for analysis.

Main Results:

• Patients with TISS <10 ng/mL (n=176) showed comparable 24-month OS (61% vs. 50%) and DFS (56% vs. 43%) to those with TISS ≥10 ng/mL (n=34), but a significantly lower RR (22% vs. 35%, P=0.031).
• Multivariable analysis indicated similar OS, DFS, RR, non-relapse mortality, and GvHD rates between TISS groups.
• A TISS ≥10 ng/mL was associated with an increased risk of viral infections (P=0.003), while FD TAC was more likely to achieve TISS <10 ng/mL (P=0.001).

Conclusions:

• Achieving a TISS <10 ng/mL early post-HCT in patients receiving PTCy/TAC prophylaxis is associated with a lower risk of viral infections and toxicities.
• This lower TISS target demonstrates similar survival outcomes compared to higher TISS levels.
• The findings suggest that targeting TISS <10 ng/mL may optimize HCT outcomes when using PTCy/TAC prophylaxis.