Favorable Adherence and Tolerability of Letermovir Versus Valganciclovir for Cytomegalovirus Prophylaxis in Kidney Transplant Recipients Aged 65 y or Older: Findings From a Randomized, Phase 3 Trial

Background. Older patients undergoing kidney transplantation are at risk of perioperative complications, underscoring the need for optimized care. The number of kidney transplants in older adults has increased in the past decade, with greater reliance on transplants from deceased donors. Methods. The phase 3, randomized, double-blind, active-controlled P002 study evaluated 200 d of letermovir versus valganciclovir prophylaxis in cytomegalovirus-seronegative kidney transplant recipients who received kidneys from cytomegalovirus-seropositive donors. Outcomes among participants aged 65 y or older are reported. Results. Forty-eight and 55 participants aged 65 y or older received letermovir or valganciclovir, respectively. A lower percentage of participants receiving letermovir versus valganciclovir had committee-confirmed cytomegalovirus disease through week 52 posttransplant (9% versus 22%; stratum-adjusted difference, –12% [95% confidence interval [CI], –27% to 2%]), without significant differences in cytomegalovirus disease or viremia between groups. A significantly higher percentage of participants receiving letermovir had ≥90% prophylaxis adherence (96% [95% CI, 86%-100%] versus 49% [95% CI, 35%-63%]). The letermovir group showed numerically lower incidences of drug-related adverse events (25% versus 49%) and study medication discontinuations due to adverse events (10% versus 20%). A significantly lower percentage of participants receiving letermovir had leukopenia or neutropenia events through week 28 posttransplant (31% [95% CI, 19%-46%] versus 62% [95% CI, 48%-75%]). Participants receiving letermovir had numerically lower rates of opportunistic infections (11% versus 25%) and rehospitalizations (51% versus 69%) through week 52 posttransplant. Conclusions. Letermovir showed substantial advantages over valganciclovir in adherence, safety, and tolerability, supporting its use as an important option for cytomegalovirus disease prophylaxis for older patients undergoing kidney transplantation. Clinical trial registration number. ClinicalTrials.gov, NCT03443869