Joseph Sassine1,2, Fareed Khawaja1, Terri Lynn Shigle3, Victoria Handy3, Farnaz Foolad1, Samuel L Aitken3, Ying Jiang1, Richard Champlin4, Elizabeth Shpall4, Katy Rezvani4, Ella J Ariza-Heredia1, Roy F Chemaly1. 1. Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 2. Division of Infectious Diseases, Department of Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA. 3. Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Abstract
BACKGROUND: Cytomegalovirus (CMV) reactivation is one of the most common infectious complications after allogeneic hematopoietic cell transplant (HCT) and may result in significant morbidity and mortality. Primary prophylaxis with letermovir demonstrated a reduction in clinically significant CMV infections (CS-CMVi) in clinical trials of CMV-seropositive HCT recipients. This study aims at exploring the effect of primary letermovir prophylaxis in this population on the incidence and outcomes of refractory or resistant CMV infections. METHODS: This is a single-center, retrospective cohort study of 537 consecutive CMV-seropositive allogeneic HCT recipients cared for between March 2016 and October 2018. Baseline demographics, HCT characteristics, CMV infections, treatment, and mortality data were collected from the electronic medical record. CMV outcomes were defined according to the recently standardized definitions for clinical trials. Characteristics and outcomes were assessed according to receipt of primary letermovir prophylaxis. RESULTS: Of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days after HCT; 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with reductions in CS-CMVi (hazard ratio [HR] 0.26; 95% confidence interval [CI], 0.16-0.41), CMV end-organ disease (HR 0.23; 95% CI, 0.10-0.52), refractory or resistant CMV infection (HR 0.15; 95% CI, 0.04-0.52), and nonrelapse mortality at week 48 (HR 0.55; 95% CI, 0.32-0.93). There was neither resistant CMV nor CMV-related mortality in the primary letermovir prophylaxis group. CONCLUSIONS: Primary letermovir prophylaxis effectively prevents refractory or resistant CMV infections and decreases nonrelapse mortality at week 48, as well as CS-CMVi and CMV disease after allogeneic HCT.
BACKGROUND: Cytomegalovirus (CMV) reactivation is one of the most common infectious complications after allogeneic hematopoietic cell transplant (HCT) and may result in significant morbidity and mortality. Primary prophylaxis with letermovir demonstrated a reduction in clinically significant CMV infections (CS-CMVi) in clinical trials of CMV-seropositive HCT recipients. This study aims at exploring the effect of primary letermovir prophylaxis in this population on the incidence and outcomes of refractory or resistant CMV infections. METHODS: This is a single-center, retrospective cohort study of 537 consecutive CMV-seropositive allogeneic HCT recipients cared for between March 2016 and October 2018. Baseline demographics, HCT characteristics, CMV infections, treatment, and mortality data were collected from the electronic medical record. CMV outcomes were defined according to the recently standardized definitions for clinical trials. Characteristics and outcomes were assessed according to receipt of primary letermovir prophylaxis. RESULTS: Of 537 patients identified, 123 received letermovir for primary prophylaxis during the first 100 days after HCT; 414 did not. In a multivariate analysis, primary prophylaxis with letermovir was associated with reductions in CS-CMVi (hazard ratio [HR] 0.26; 95% confidence interval [CI], 0.16-0.41), CMV end-organ disease (HR 0.23; 95% CI, 0.10-0.52), refractory or resistant CMV infection (HR 0.15; 95% CI, 0.04-0.52), and nonrelapse mortality at week 48 (HR 0.55; 95% CI, 0.32-0.93). There was neither resistant CMV nor CMV-related mortality in the primary letermovir prophylaxis group. CONCLUSIONS: Primary letermovir prophylaxis effectively prevents refractory or resistant CMV infections and decreases nonrelapse mortality at week 48, as well as CS-CMVi and CMV disease after allogeneic HCT.
Authors: Marcie Tomblyn; Tom Chiller; Hermann Einsele; Ronald Gress; Kent Sepkowitz; Jan Storek; John R Wingard; Jo-Anne H Young; Michael J Boeckh; Michael A Boeckh Journal: Biol Blood Marrow Transplant Date: 2009-10 Impact factor: 5.742
Authors: Roy F Chemaly; Lynn El Haddad; Drew J Winston; Scott D Rowley; Kathleen M Mulane; Pranatharthi Chandrasekar; Robin K Avery; Parameswaran Hari; Karl S Peggs; Deepali Kumar; Rajneesh Nath; Per Ljungman; Sherif B Mossad; Sanjeet S Dadwal; Ted Blanchard; Dimpy P Shah; Ying Jiang; Ella Ariza-Heredia Journal: Clin Infect Dis Date: 2020-12-03 Impact factor: 9.079
Authors: Prashant Sharma; Neel Gakhar; Jennifer MacDonald; Maheen Z Abidi; Esther Benamu; Valida Bajrovic; Enkhtsetseg Purev; Bradley M Haverkos; Jennifer Tobin; Jeff Kaiser; Stephanie Chase; Matthew Miller; Adriana Weinberg; Jonathan A Gutman Journal: Bone Marrow Transplant Date: 2019-10-29 Impact factor: 5.483
Authors: N G Almyroudis; A Jakubowski; D Jaffe; K Sepkowitz; E Pamer; R J O'Reilly; G A Papanicolaou Journal: Transpl Infect Dis Date: 2007-05-19 Impact factor: 2.228