Johnsrud JJ, et al. Biol Blood Marrow Transplant 2020.
Despite effective therapies, CMV continues to have a significant impact on morbidity and mortality in hematopoietic cell transplant recipients. At particular risk are recipients of alternative grafts such as umbilical cord blood (UCB), haploidentical transplants (haplo), or patients conditioned with T-cell depleting regimens such as anti-thymocyte globulin (ATG). With the approval of letermovir, its impact on high risk patients is of particular interest. To evaluate the impact of letermovir prophylaxis at our center we performed a retrospective analysis of 114 high risk patients who received letermovir as prophylaxis (LET PPX) between January 2018 through December 2019, including 30 UCB and 22 haplo recipients, compared to 637 historical controls with comparable risk between January 2013 and December 2019. By D+100, letermovir prophylaxis significantly decreased the incidence of both CMV DNAemia compared to controls (45.37% vs 74.1%; P <.001) and clinically significant CMV infection (12.04% vs 48.82%; P <.001). The impact of LET PPX was even more profound on the incidence of clinically significant CMV infection (CSI) defined as the administration of antiviral therapy either as preemptive therapy for CMV DNAemia or treatment for CMV disease. CSI was significantly lower in haplo recipients on LET PPX compared to controls (13.64% vs 73.33%; P= .02) and UCB recipients on LET PPX compared to controls (3.45% vs 37.5%; P <.001). No patients on LET primary PPX developed CMV disease in any treatment group by D+100, compared to controls (0% vs 5.34%, respectively; P= .006). Patients on LET PPX had fewer hospitalizations involving initiation of anti-CMV therapy compared to controls (0.93% vs 15.23%, respectively). Our analysis of the largest cohort of patients at high risk for CMV reactivation published to date demonstrates that letermovir prophylaxis significantly reduces the number of patients who receive CMV-active antiviral therapy for either DNAemia or disease due to CMV.