(223) Tacrolimus Time in Therapeutic Range after Hematopoietic Stem Cell Transplantation

Poster Abstract:

Background: Tacrolimus, a calcineurin inhibitor, is often used in combination with other immunosuppressive agents to prevent graft versus host disease (GVHD) in patients receiving allogeneic hematopoietic stem cell transplant (HSCT). Tacrolimus trough levels are monitored after HSCT due to its narrow therapeutic index. Subtherapeutic tacrolimus levels increase the risk of developing GVHD, and supratherapeutic levels increase the risk of toxicities such as acute kidney injury (AKI) and posterior reversible encephalopathy syndrome (PRES). Additionally, tacrolimus metabolism is reliant on Cytochrome P450 3A4 (CYP3A4) resulting in several drug interactions and adding to the complexity of dosing. An optimal tacrolimus therapeutic range for allogeneic HSCT patients is not well defined, representing a gap in data. Therapeutic ranges are institution-specific and heavily influenced by provider experience.

Objectives: The purpose of this study is to assess clinical outcomes associated with tacrolimus levels within the first 6 months following allogeneic HSCT and to identify a preferred goal range for tacrolimus levels that optimizes efficacy (preventing GVHD) and safety (adverse drug events).

Methods: This is a single-center, retrospective chart review. Adult patients are included if they received tacrolimus for GVHD prophylaxis following allogeneic HSCT at UHCMC between 4/1/2018 and 4/1/2023. Patients are excluded if they received a syngeneic HSCT, a CD34 selected graft, or had a prior allogeneic HSCT. We expect to include 150 patients. The primary outcome is the incidence of GVHD within 6 months following allogeneic HSCT. Secondary outcomes include time to incidence of GVHD, time within pre-defined therapeutic tacrolimus ranges (8-13 ng/mL at months 1-3 and 5-8 ng/mL at months 4-6), and average tacrolimus level within 6 months of allogeneic HSCT. Safety outcomes include incidence of AKI, PRES, all-cause mortality, and tacrolimus discontinuation within 6 months of allogeneic HSCT.

Results: Results will be presented at the 2024 HOPA Annual Conference.
Discussion/

Conclusion: Discussion and conclusions will be presented at the 2024 HOPA Annual Conference.

References (must also be included in final poster): 1. Bolaños-Meade J, et al. Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med. 2023 Jun 22;388(25):2338-2348.
2. Yao JM, et al. Tacrolimus initial steady state level in post-transplant cyclophosphamide-based GvHD prophylaxis regimens. Bone Marrow Transplant. 2022 Feb;57(2):232-242.
3. Soskind R, et al. Initial tacrolimus weight-based dosing strategy in allogeneic hematopoietic stem-cell transplantation. J Oncol Pharm Pract. 2021 Sep;27(6):1447-1453.
4. Penack O, et al. Prophylaxis and management of graft versus host disease after stem-cell transplantation for hematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol. 2020 Feb;7(2):e157-e167.
5. Bolaños-Meade J, et al. Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with hemopoietic cell transplantation with reduced-intensity conditioning: a randomized phase 2 trial with a non-randomized contemporaneous control group (BMT CTN 1203). Lancet Haematol. 2019 Mar;6(3):e132-e143.
6. Yu J, et al. Mortality, length of stay and costs associated with acute graft-versus-host disease during hospitalization for allogeneic hematopoietic stem cell transplantation. Curr Med Res Opin. 2019 Jun;35(6):983-988.