Oral Vs Intravenous Tacrolimus Post Allogeneic Stem Cell Transplant: A Retrospective Analysis

Abstract

Introduction Tacrolimus (tacro) is commonly used for the prevention of graft vs host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). Due to concerns of inadequate absorption, tacro is commonly administered intravenously (IV) in the immediate post allogeneic transplant period. Advantages to oral (PO) tacro include decreased need for multi lumen IV catheters, improved patients (pts) convenience, and reduced cost. We retrospectively analyzed differences in safety, tolerability, time to achieve therapeutic levels during the 1st 4 weeks and rates of acute GVHD. Methods IV tacro at 0.02 mg/kg by continuous infusion or PO tacro at 0.03 mg/kg twice daily was started between T-3 and T+5. Levels were assessed 3 times weekly. Dose was titrated to achieve a steady level between 7 and 14 ng/ml. GVHD was graded according to CIBMTR criteria. Results 54 pts were treated between Sep 2016 and July 2018. 21 who received PO tacro and 27 who received IV tacro were studied. 6 pts on PO tacro are still within 100 days post-transplant and will be reported in follow up. The median age was 59 years (range, 21-74), 52% were females, diagnoses were AML (54%), MDS (19%), ALL (15%), CML (6%), NHL (4%) and MF (2%). HCT-CI was 0, 1-3 and >3 in 23%, 54% and 23% of pts, respectively. Donors were match-unrelated (58%), match-related (27%), haploidentical (6%) and double umbilical cord (6%). Conditioning regimens were myeloablative (60%) and reduced intensity (40%). 60% of pts received rabbit ATG (3 mg/Kg). GVHD prophylaxis also included mini-MTX on days +1, +3, +5 and +11 (79%), MMF (15%), and MMF + post-transplant Cy (6%). Pts characteristics were similar between the 2 groups. 7 pts (33%) who initially started on PO tacro switched to IV due to poor absorption (3), mucositis (1), toxicity (1), GVHD (1) and patient's concern (1). Target therapeutic level was reached in 67% vs 81% during week 1, 86% vs 96% during week 2, 95% vs 96% during week 3, and 100% vs 96% during week 4, of pts on PO vs IV tacro, respectively. Median tacro level during the 1st 4 weeks was 12.6 ng/ml vs 11.2 ng/ml, acute kidney injury occurred in 23.8% vs 33.3% (p=.47) and increased bilirubin occurred in 4.7% vs 22.2% (p=.09), in pts on PO vs IV tacro. Posterior reversible encephalopathy was observed in 1 patient on PO tacro. Grade I and Grade II-IV acute GVHD incidence was 47.6% vs 14.8% (p=.01) and 47.6% vs 44.4% (p=.82) of pts on PO vs IV tacro. Stage 1-2 skin aGVHD rate was higher in the PO vs. IV group (90% vs 33.3%; p=.0001). There was no difference in rates of stage 3 skin (4.7% vs 3.7%), stage 1 GI (33.3% vs 33.3%), or stage 2-4 GI (14% vs 7.4%) aGVHD. None of the pts had stage 4 skin or any stage liver aGVHD. Conclusion PO tacro is safe and effective in the prevention of aGVHD in pts receiving myeloablative or RIC allo-SCT. The use of PO tacro during the 1st 4 weeks post-transplant was found to be associated with higher rate of stage 1-2 skin aGVHD and warrants further study.