Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Purpose: Evaluation of mammalian target of rapamycin inhibitor (mTORi)-related adverse events (AEs) and drug trough levels (C0) at onset may aid their management in liver transplant recipients (LTRs). Here, we investigate time to onset, drug C0, and related discontinuations due to select mTORi (everolimus [EVR])-associated AEs from the pivotal H2304 (NCT00622869) study.
Methods: In this 24-month, multicenter, open-label, controlled study, de novo LTRs were randomized (1:1:1) at 30 (±5) days posttransplant to EVR+rTAC (EVR C0: 3-8 ng/mL; tacrolimus (TAC) C0: 3-5 ng/mL); TAC withdrawal (EVRmono [EVR C0: 6-10 ng/mL; TAC withdrawal by Month 4]); or TAC control (TAC-C: C0: 6-10 ng/mL) arms. Time to onset from randomization, EVR C0 at onset (before/at/after event), and reported rates of concomitant medication use and treatment discontinuation for hyperlipidemia, proteinuria, stomatitis, and wound healing events (WHE) were assessed.
Results: Hyperlipidemia was the most frequent AE in all 3 arms. Median onset time of WHE was shorter than that of the other 3 AEs in both EVR arms, whereas that of hyperlipidemia was shortest in TAC-C arm. Median EVR C0 at onset in the EVR arms was within target range regardless of AE. Median TAC C0 at onset was above (hyperlipidemia and proteinuria) or near (stomatitis and wound healing) the upper limit of target range in the EVR+rTAC arm. In the EVRmono arm, median onset time of all AEs, except proteinuria (198 days), was shorter than the TAC discontinuation target of 4 months. In both EVR arms, most hyperlipidemia, stomatitis, and wound healing (70%-77%) events were treated with concomitant medications. Events requiring treatment discontinuation were low (0%-8%), except for proteinuria in the EVR+rTAC (8/13; 61.5%) and EVRmono (3/12; 25%) arms.
Conclusion: In LTRs receiving EVR-based regimens, most related AEs could be managed by adjusting of EVR C0 and/or use of concomitant medications. Treatment discontinuation was mostly required with proteinuria.
CITATION INFORMATION: Fung J., Saliba F., Schlitt H., Junge G., McCague K., Patel D., Charlton M. Association between Everolimus Trough Levels, Onset of Related Adverse Events, and Treatment Discontinuation after Liver Transplantation: 24-Month Results from the H2304 Study Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Fung J, Saliba F, Schlitt H, Junge G, McCague K, Patel D, Charlton M. Association between Everolimus Trough Levels, Onset of Related Adverse Events, and Treatment Discontinuation after Liver Transplantation: 24-Month Results from the H2304 Study [abstract]. https://atcmeetingabstracts.com/abstract/association-between-everolimus-trough-levels-onset-of-related-adverse-events-and-treatment-discontinuation-after-liver-transplantation-24-month-results-from-the-h2304-study/. Accessed June 25, 2019.
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