MK-8228-002 post hoc analysis: Impact of kidney function on CMV prophylaxis after kidney transplantation

The phase III, randomized, double-blind, double-dummy, multicenter MK-8228-002 trial (NCT03443869) compared letermovir with valganciclovir for 200 days of cytomegalovirus (CMV) prophylaxis in adult CMV-seronegative kidney transplant recipients (KTRs) receiving organs from CMV-seropositive donors (D+R−). A post hoc analysis evaluated the impact of kidney function, assessed by Cockcroft–Gault creatinine clearance (CrCl), on CMV prophylaxis outcomes, including dosing patterns, adherence, quantifiable CMV (qCMV) DNAemia, and prophylaxis discontinuations. Results were published in the American Journal of Transplantation by Budde et al. Data on 480 KTRs were reported (letermovir, n = 233; valganciclovir, n = 247).

Key data: All participants receiving letermovir remained on once-daily dosing through Week 28, while approximately 50% of those receiving valganciclovir required intermittent dosing based on CrCl. Intermittent valganciclovir dosing was associated with lower adherence compared with once-daily dosing. qCMV DNAemia through Week 28 was numerically higher with valganciclovir among patients with CrCl ≤67 and >67 mL/min (13.1% and 4.3%, respectively), compared with letermovir (1.7% and 2.6%, respectively). Confirmed CMV disease through Week 28 occurred in 3.1% and 0% of valganciclovir- and letermovir-treated patients with CrCl ≤67 mL/min, respectively. Prophylaxis discontinuations for any reason were more frequent with valganciclovir in patients with CrCl ≤67 vs >67 mL/min (23.1% vs 10.3%); 4.3% of patients with CrCl ≤67 mL/min discontinued letermovir.

Key learning: This post hoc analysis indicates that kidney function influences dosing patterns, adherence, and CMV prophylaxis outcomes, with differing patterns observed between letermovir- and valganciclovir-based treatment, highlighting renal function as an important consideration when selecting CMV prophylactic strategies in D+R− KTRs.