Tacrolimus and Everolimus Against Mycophenolate Mofetil to Prevent Major Adverse Transplant Events in Pediatric Heart Transplant - TEAMMATE
Contribution To Literature:
The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given ≥6 months after cardiac transplantation.
The goal of the trial was to evaluate everolimus with low-dose tacrolimus compared with tacrolimus with mycophenolate among young patients who were ≥6 months after cardiac transplantation. The Food and Drug Administration previously issued a black box warning when everolimus was used within 3 months of cardiac transplant. The warning was due to a higher risk of mortality due to early infection.
Children and young adults after cardiac transplant were randomized to everolimus with low-dose tacrolimus (n = 107) vs. tacrolimus with mycophenolate (n = 104).
- Total number of enrollees: 211
- Duration of follow-up: 30 months
- Mean patient age: 7 years
- Percentage female: 50%
- Cardiac transplantation at age ≤21 years
- ≥6 months after heart transplantation
- Stable immunosuppression
- Recurrent rejection/graft dysfunction
- Steroid dose >0.1 mg/kg/day
- Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2
- Active infection or wound healing problem
- Severe hyperlipidemia or proteinuria
The primary efficacy outcome was defined by the major adverse transplant event (MATE) score (points assigned for each of the following; cardiac allograft vasculopathy, renal dysfunction, acute cellular rejection, antibody-mediated rejection, infection, or post-transplant lymphoproliferative disorder). MATE-6 considered all of these outcomes, while MATE-3 considered cardiac allograft vasculopathy, renal dysfunction, acute cellular rejection.
- The co-primary outcome, median MATE-6 score at 30 months, was 1.96 in the everolimus group vs. 2.18 in the tacrolimus group (p = not significant [NS]).
- The co-primary outcome, median MATE-3 score at 30 months, was 0.93 in the everolimus group vs. 1.25 in the tacrolimus group (p = NS).
- Of the MATE-6 components, the everolimus group had numerically lower cardiac allograft vasculopathy, renal dysfunction, and rejection. The everolimus group had numerically higher infection and lymphoproliferative disorder.
- Of the MATE-3 components, the everolimus group had numerically lower cardiac allograft vasculopathy, and renal dysfunction. The everolimus group had numerically higher cellular rejection.
- Median MATE-3 score + cytomegalovirus infection at 30 days: 1.06 in the everolimus group vs. 1.51 in the tacrolimus group (p = 0.03)
- eGFR was higher in the everolimus vs. tacrolimus group (p < 0.05)
- Percentage with anti-HLA antibodies was lower in the everolimus vs. tacrolimus group (p < 0.05)
- Drug discontinuation due to adverse event: 12% with everolimus vs. 21% with tacrolimus (p < 0.001)
Among children and young adults with cardiac transplantation, everolimus with low-dose tacrolimus compared with tacrolimus with mycophenolate was safe when initiated 6 months after cardiac transplant. In the present trial, everolimus with low-dose tacrolimus was also associated with higher eGFR and lower anti-HLA antibody compared with tacrolimus with mycophenolate.
Presented by Dr. Christopher Almond at the American Heart Association Scientific Sessions, Philadelphia, PA, November 11, 2023.
Keywords: AHA23, Heart Transplantation, Immunosuppression Therapy, Pediatric Cardiology
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