Kathleen A Linder1, Christopher Kovacs2, Kate M Mullane3, Cameron Wolfe4, Nina M Clark5, Ricardo M La Hoz6, Jeannina Smith7, Camille N Kotton8, Ajit P Limaye9, Maricar Malinis10, Morgan Hakki11, Aaron Mishkin12, A Adrian Gonzalez13, Maria Dioverti Prono14, Darin Ostrander14, Robin Avery14, Daniel R Kaul1. 1. University of Michigan, Ann Arbor, MI, United States. 2. Cleveland Clinic, Cleveland, OH, United States. 3. University of Chicago, Chicago, IL, United States. 4. Duke University, Durham, NC, United States. 5. Loyola University, Chicago, IL, United States. 6. University of Texas Southwestern Medical Center, Dallas, TX, United States. 7. University of Wisconsin, Madison, WI, United States. 8. Massachusetts General Hospital, Boston, MA, United States. 9. University of Washington, Seattle, WA, United States. 10. Yale, New Haven, CT, United States. 11. Oregon Health and Science University, Portland, OR, United States. 12. Temple University, Philadelphia, PA, United States. 13. West Coast ID, Safety Harbor, FL, United States. 14. Johns Hopkins University, Baltimore, MD, United States.
Abstract
BACKGROUND: Few options are available for Cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients. METHODS: Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected. RESULTS: Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. 45/47 (94%) were treated with other agents prior to LET and 57% had a history of prior CMV disease. 77% were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load (VL) <1000 IU/ml at LET initiation, 2 experienced >1log rise in VL by week 12 and no deaths were attributed to CMV. Ten patients had VL >1000 IU/ml at LET initiation, and 6/10 (60%) had a CMV viral load <1000 IU/ml at completion of therapy or last known value. LET was discontinued in 2 patients for an adverse event. CONCLUSIONS: Patients treated with LET with viral load <1000 IU/ml, had good virologic outcomes. Outcomes were mixed when LET was initiated at higher viral loads. Further studies on combination therapy or alternative LET dosing are needed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
BACKGROUND: Few options are available for Cytomegalovirus (CMV) treatment in transplant recipients resistant, refractory, or intolerant to approved agents. Letermovir (LET) is approved for prophylaxis in hematopoietic cell transplant (HCT) recipients, but little is known about efficacy in CMV infection. We conducted an observational study to determine the patterns of use and outcome of LET treatment of CMV infection in transplant recipients. METHODS:Patients who received LET for treatment of CMV infection were identified at 13 transplant centers. Demographic and outcome data were collected. RESULTS: Twenty-seven solid organ and 21 HCT recipients (one dual) from 13 medical centers were included. 45/47 (94%) were treated with other agents prior to LET and 57% had a history of prior CMV disease. 77% were intolerant to other antivirals; 32% were started on LET because of resistance concerns. Among 37 patients with viral load (VL) <1000 IU/ml at LET initiation, 2 experienced >1log rise in VL by week 12 and no deaths were attributed to CMV. Ten patients had VL >1000 IU/ml at LET initiation, and 6/10 (60%) had a CMV viral load <1000 IU/ml at completion of therapy or last known value. LET was discontinued in 2 patients for an adverse event. CONCLUSIONS:Patients treated with LET with viral load <1000 IU/ml, had good virologic outcomes. Outcomes were mixed when LET was initiated at higher viral loads. Further studies on combination therapy or alternative LET dosing are needed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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Keywords:
cytomegalovirus infection; letermovir; solid organ transplantation; stem cell transplantation