LB21. Preemptive Therapy (PET) vs. Prophylaxis for Prevention of Cytomegalovirus (CMV) Disease in High-Risk Donor Seropositive/Recipient Seronegative (D+R−) Liver Transplant Recipients (LTR): A NIH-Sponsored, Randomized, Controlled, Multicenter Trial

Abstract Background Current guidelines preferentially recommend valganciclovir (VGCV) prophylaxis over PET in most D+R− organ transplant populations, but adequately powered direct comparative clinical trials are lacking. Methods D+R− LTR were randomly assigned (1:1, stratified by site and T-cell depleting induction) to receive either PET (weekly plasma CMV DNAemia at central laboratory for 100 days, with VGCV 900 mg bid for DNAemia at any level, until two consecutive negative weekly tests) or prophy (VGCV 900 mg qd for 100 days). The primary outcome was CMV disease by 12 months as adjudicated by an independent, blinded, endpoint committee in ITT population. Secondary outcomes were opportunistic infections (OIs) (invasive fungal and bacterial), neutropenia (ANC < 1000/µL), acute rejection, graft loss, and mortality assessed at12 months. Results From October 2012 to June 2017, 205 patients were randomized at six centers; 100 to PET, 105 to prophy. The incidence of CMV disease was 9% (9/100) in PET and 19% (20/105) in prophy (P = 0.039) with majority of difference due to post-prophylaxis disease: 6% in PET vs. 17% in prophy (P = 0.027). CMV disease included syndrome in 55% (16/29) and end-organ in 45% (13/29), with similar proportions in two groups. Secondary outcomes were not different for PET and prophy groups: OIs (19% vs. 21%), neutropenia (34% vs.. 28%), acute rejection (27% vs. 27%), graft loss (2% vs. 2%), and mortality (10% vs. 6%), respectively, P > 0.05 for all comparisons. Mortality at last follow-up (median 3.2 years) was not different for PET vs. prophy (14% vs. 18%, P = 0.43). Conclusions PET significantly reduced the incidence of CMV disease compared with prophy in D+R- LTR, and was associated with similar other clinical outcomes. Current guidelines should be revised to recommend PET over prophylaxis in this setting, and similar trials conducted in other D+R− transplant populations. (Funded by NIAID; ClinicalTrials.gov# NCT01552369.) Disclosures D. Winston, Merck: Investigator, Research support. Chimerix: Investigator, Research support. Shire: Investigator, Research support. Gilead: Investigator, Research support. Oxford Immunotech: Investigator, Research support. G. M. Lyon III, Shire: Investigator, institutional research support. Hookipa: Investigator, institutional research support. Merck: Investigator, institutional research support. F. P. Silveira, Shire: contracted clinical research, site investigator. A. P. Limaye, Merk: Consultant and Investigator, Consulting fee and Research grant. Astellas Pharma Inc.: Consultant and Investigator, Consulting fee. Helocyte Inc.: Consultant, Consulting fee.