Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation.

BACKGROUND: Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS: 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS: LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION: LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

Rejection! Or is it? Correlation among molecular microscope diagnostic system, histopathology and clinical judgement following heart transplantation.

PURPOSE: Little is known about clinical decision making among discordant findings concerning for rejection with endomyocardial biopsy (EMBx) and Molecular Microscope Diagnostic System (MMDx) in patients following heart transplantation. METHODS: Two hundred and twenty-eight corresponding EMBx and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed. Rejection was classified as t-cell mediated rejection ≥2R and/or antibody mediated rejection ≥1. Clinical decision making among concordant and discordant cases of EMBx and MMDx results were reviewed. RESULTS: Patient characteristics were comparable between concordant and discordant patient groups (median age 60 yrs., 76% male, and 71% White). A total of 167/228 specimens (73%) were concordant for no rejection with 98% agreement in clinical decision making and 25/228 (11%) concordant for rejection with 64% agreement in clinical decision making. Among the 36/228 (16%) discordant samples, clinical decision-making agreed on treatment for rejection in five of the MMDx samples and three of the EMBx samples. CONCLUSIONS: MMDx can be an additional tool to diagnose rejection not detected by the traditional EMBx and influence clinical decision making in guiding appropriate treatment. Ongoing investigation into the clinical utility of MMDx is warranted to determine the significance of discordant findings among diagnostic modalities when assessing for rejection.