PGY2 Oncology Resident Geisinger Danville, Pennsylvania, United States
Poster Abstract: Cytomegalovirus (CMV) remains one of the most common infections in patients receiving an allogenic hematopoietic stem cell transplant (alloHSCT). Due to complications with this infection, management consists of prophylaxis, pre-emptive, and treatment therapy. Letermovir is an antiviral agent that binds to components of CMV terminase complex, thereby inhibiting CMV replication. Letermovir was FDA approved for prophylaxis use in CMV-seropositive alloHSCT recipients through Day +100 (week 14) in 2017. It remains unclear if the CMV risk persists beyond the Day +100 prophylaxis period; however, in the registration study for letermovir, the incidence of CMV reactivation increased significantly between week 14 and week 24.1 A current phase 3 trial evaluated whether extending CMV prophylaxis with letermovir from 100 days to 200 days post-HSCT resulted in additional benefit compared to placebo in patients at high risk for clinically significant CMV infection (CS-CMVi) beyond 100-days post-HSCT.2 This trial met its primary endpoint, which was the proportion of participants with CS-CMVi from week 14 (~100 days) through week 28 (~200 days) post-HSCT. Two studies concluded that PTCy, regardless of donor, is associated with higher incidence in CS-CMVi, augmenting the risk of CMV-seropositivity.3, 4 Currently, at Geisinger Cancer Institute, the standard of care for GVHD prevention is post-transplant cyclophosphamide (PTCy) and cyclosporine, making our patients at a greater risk for reactivation. The goal of this study is to evaluate the occurrence of CMV reactivation and CS-CMVi to determine if it is occurring in seropositive donor transplants due to increased risk with PTCy, and if extended letermovir yields benefit.
Data was collected from the electronic medical record from 06/01/2013 - 06/30/2023 for patients 18 years or older who are CMV seropositive from recipient, donor, or both that received an alloHSCT. The primary endpoint is the difference in occurrence of CMV reactivation and CS-CMVi for donor compared to recipient CMV seropositive alloHSCT patients. Secondary endpoints include the difference in CMV reactivation for patients utilizing letermovir prophylaxis compared to those that did not and between those utilizing letermovir prophylaxis up to Day +100 post-transplant compared to those continued past Day +100. CMV reactivation is defined as two consecutive CMV levels ≥ 150 copies/ml. CS-CMVi will also be evaluated in this study, which is defined as CMV detected from an organ system by biopsy or other invasive procedure with sufficient sensitivity and specificity in combination with signs and/or symptoms from organ disease.
Results and conclusions are pending for this study.
References (must also be included in final poster): 1. Marty FM, Ljungman P, Chemaly RF, et al. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017;377(25):2433-2444. doi:10.1056/NEJMoa1706640. 2. A Phase 3 Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Letermovir (LET) Prophylaxis When Extended From 100 Days to 200 Days Post-transplant in Cytomegalovirus (CMV) Seropositive Recipients (R+) of an Allogenic Hematopoietic Stem Cell Transplant (HSCT). ClinicalTrials.gov identifier: NCT03930615. Updated November 1, 2022. Accessed December 18, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03930615 3. Liu LW, Yn A, Gao F, et al. Letermovir Discontinuation at Day 100 After Allogeneic Stem Cell Transplant Is Associated With Increased CMV-Related Mortality. Transplant Cell Ther. 2022;28(8):510.e1-510.e9. doi:10.1016/j.jtct.2022.05.020 4. Goldsmith SR, Abid MB, Auletta JJ, et al. Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis. Blood. 2021;137(23):3291-3305. doi:10.1182/blood.2020009362.
