Optimization of Tacrolimus Serum Levels When Combined with Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis after Hematopoietic Cell Transplantation: Outcome Data Analysis

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.4518-4518
• Main Authors: Yao, Janny M., Yang, Dongyun, Mokhtari, Saloomeh, Salhotra, Amandeep, Ali, Haris, Arslan, Shukaib, Otoukesh, Salman, Aldoss, Ibrahim, Sandhu, Karamjeet S., Stein, Anthony, Snyder, David, Pullarkat, Vinod A., Marcucci, Guido, Forman, Stephen J, Nakamura, Ryotaro, Al Malki, Monzr M.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-129221

Post-transplant cyclophosphamide (PTCy) in combination with tacrolimus and mycophenolate mofetil (MMF) has been used increasingly in recent years to prevent graft-versus-host disease (GvHD) in patients undergoing hematopoietic cell transplantation (HCT), and has been proven safe and effective regardless of HLA matching criteria. Historically, the therapeutic dose level recommended for tacrolimus has ranged from 10 to 15 ng/mL, when combined with methotrexate, and between 5-10 ng/mL when combined with sirolimus. However, data on the optimal starting dose and serum level of tacrolimus when combined with PTCy does not exist. Given tacrolimus's broad inhibition on T-cells activation and the PTCy's selective inhibition on alloreactive T-cells, we hypothesized that lower serum levels of tacrolimus could suffice to achieve optimal transplant outcomes. We retrospectively identified a consecutive case series of 219 patients who received HCT with PTCy (50 mg/kg on days +3 and +4) in combination with tacrolimus and MMF (day +5) as GvHD prophylaxis at City of Hope from January 2011 to June 2018. Tacrolimus was delivered with continuous intravenous infusion until engraftment, then switched to equivalent oral dose. Tacrolimus dosing was weight-based (WBD) in 80 patients and fixed dose (FD) of 1 mg in 139 patients. We captured Tacrolimus levels at two different time points: 1. the initial steady state (ISS) and 2. at engraftment level (EL) to identify which time point will correlate with better HCT outcomes. At each time point, transplant outcomes were compared between patients with serum levels ≥10 ng/mL and