Introduction

mTORi's reduce BKV large T antigen expression in vitro and are associated with lower rates of BKV infection in clinical studies.

Methods

Pilot single center, randomized, open-label trial comparing the safety and efficacy of MMF discontinuation with the addition of everolimus (Group 1; n=20) vs a 50% reduction of MMF (Group 2; n=20) in patients with new onset BK viruria >1 million copies/mL and/or viremia >500 copies/mL. Patients on maintenance IS with TAC, MMF, and prednisone are eligible; prednisone is continued at the same dose. TAC trough goals are 3-6 and 4-10 ng/mL for Groups 1 and 2, respectively. Everolimus trough goal is 3-8 ng/mL. Primary endpoint is a >50% reduction of BK viruia and/or clearance of viremia at 3-months post-randomization, secondary endpoint is the % reduction in BK viremia at 3-months.

Results

Thus far 18 and 19 patients completed the study protocol in Groups 1 and 2, respectively. Baseline characteristics including rates of depleting antibody induction were similar between the groups. Mean POD of BK diagnosis was 111.4 and 130.8 for Groups 1 and 2, respectively. Drug exposure, kidney function and BKV levels at enrollment and month 3 are listed in the Table.

44.4% and 36.8% of patients in Groups 1 and 2 met the primary study end point, respectively (P=0.74). The % reduction in BK viremia was 66.6 and 48.7 for Groups 1 and 2, respectively (P=0.3). Urine protein excretion was unchanged; total cholesterol rose from 178 to 209 mg/dL in Group 1 patients (P=0.045). Two patients in Group 1 were converted back to MMF for elevated LFTs (1) and GI intolerance (1). There was 1 case of rejection in Group 2 and 2 patients in each group had BKVAN on a protocol biopsy.

Conclusion

Everolimus conversion for the treatment of BKV infection is promising but did not reach statistical significance. Expansion of this study to its powered number of 60 is necessary to further define the efficacy of this strategy.

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