Introduction: CTLA4Ig is a novel IS agent that acts through costimulatory blockade of T-cells and obviates the need for CNI. Despite benefits in improving renal function, CTLA4Ig therapy is associated with an increased risk for PTLD despite limiting use to pts who are EBV sero(+). Here we examined the risk for EBV and other viral infections in pts receiving CTLA4Ig- vs. CNI-IS. Methods: The incidence of EBV, CMV, BKV viremia (by PCR), PTLD and BK associated nephropathy (BKAN) were compared in 39 CTLA4Ig- vs. 1011 CNI-IS-treated pts. CMV-specific memory T cell levels (CMV-T) by intracellular cytokine flow cytometry were tested in 9 CTLA4Ig-treated pts. All pts were >18 years and 40% of those were HLA-sensitized. The median follow-up was 18.2M post-transplant and the median duration of CTLA4Ig treatment 19.1M. Results: The results are shown in the Table. Briefly, there was no significant difference in the CMV and BKV viremia rate and peak viral levels between the two groups. In addition, no pt in the CTLA4Ig group developed BKAN. In contrast, the incidence of EBV viremia (15.4% vs. 3.3%, p<0.0001) and PTLD (7.7% vs. 0%, p<0.0001) in the CTLA4Ig group were significantly higher than the CNI-IS group. In addition, the EBV levels at onset of PTLD were only 41.3±14.3 copies/PCR. Two of the PTLD cases were CNS based and resulted in deaths, both occurring <1.5 years post-CTLA4Ig therapy. CMV-T was detected in all CMV sero(+) CTLA4Ig-treated pts, suggesting no effect of CTLA4Ig on CMV-T function. Data for EBV-T is not known. Conclusions: CTLA4Ig-treated pts were not at increased risk for CMV or BKV viremia or BKAN. However, there was a significant risk for EBV viremia and PTLD in this group compared to CNI-IS group. At this point, the mechanism(s) are unclear. However, these findings suggest increased vigilance for EBV-PCR(+) is warranted. Early treatment with IVIG+ACV may be helpful.

CITATION INFORMATION: Shin B, Choi J, Kahwaji J, Ge S, Thomas D, Vo A, Galera O, Villicana R, Peng A, Jordan S, Toyoda M. Examining the Risk for Post-Transplant Viral Infections and Lymphoproliferative Disorder (PTLD) in Kidney Transplant Patients (Pts) Receiving Calcineurin Inhibitor-Based Immunosuppression (CNI-IS) Compared to Belatacept (CTLA4Ig). Am J Transplant. 2016;16 (suppl 3).

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