793 - Mammalian Target of Rapamycin Inhibitor Initiation is Associated with Increased Risk of Molecular and Histological Rejection

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Author Block: A. Kanelidis¹, A. Guha², A. Bhimaraj², A. Vaidya³, A. Nguyen¹, S. Nathan⁴, C. Fan⁵, J. Kobulnik⁵, K. Oreschak⁵, L. Shen⁵, S. Hall⁶, ¹University of Chicago, Chicago, IL, ²Houston Methodist, Houston, TX, ³USC, Los Angeles, CA, ⁴Memorial Hermann, Houston, TX, ⁵CareDx, Brisbane, CA, ⁶Baylor University Medical Center, Dallas, TX
*Purpose: Mammalian target of rapamycin inhibitor (mTORi) initiation may be associated with rejection risk but there is a dearth of data in a large real-world contemporary heart transplant (HT) population. We sought to assess the cumulative incidence of molecular evidence of rejection [gene expression profiling (GEP) and donor derived cell-free DNA (dd-cfDNA)] and clinical events after mTORi initiation in patients enrolled in the Surveillance HeartCare Outcomes Registry (SHORE).
*Methods: Patients initiated on mTORi 2-months to 5-years post-HT were propensity matched in a 1:2 ratio with controls (patients not taking mTORi at the time of matching). The cumulative incidence of 1) simultaneous dd-cfDNA (≥0.20%) and GEP (≥30, 2-6 months; ≥34, 6+ months post-HT) elevation; 2) rejection on biopsy (acute cellular rejection ≥2R and/or ≥pAMR1); 3) cardiac allograft vasculopathy (CAV grade 2 or 3) and 4) graft dysfunction (LVEF <50%) and cardiovascular death were compared between groups in the 24 months following mTORi initiation.
*Results: This analysis included 663 patients initiated on mTORi and 1266 controls matched by recipient and donor age and sex, transplant date, history of CAV, number of graft dysfunction and rejection episodes, and recipient race. Median (IQR) time to mTORi initiation was 442 (253-643) days post-HT. When compared to controls, patients initiated on mTORi had a higher cumulative incidence of future rejection (10.2% vs 6.6%; p=0.006, Figure A) and future dd-cfDNA+/GEP+ (20.1% vs 15.5%; p=0.043, Figure B). There was no significant difference in CAV2/3 (p=0.59) or graft dysfunction and cardiovascular death (p=0.52) in the 24-month follow-up period between groups.
*Conclusions: Patients initiated on mTORi have increased evidence of molecular and histological rejection compared to controls. More frequent non-invasive monitoring to detect early changes in immune activation and graft injury may be warranted in this population.