Multinational Study Assessing Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Hematopoietic Stem Cell Transplant Recipients with Cytomegalovirus Infection and Intolerance to Anti-Cytomegalovirus Therapies

Management of cytomegalovirus (CMV) infection after hematopoietic stem cell transplant (HSCT) can be limited by intolerance due to related toxicities of ganciclovir, valganciclovir or foscarnet. To describe real-world treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among HSCT recipients with CMV infection and intolerance to anti-CMV agents. This multicenter, retrospective study used de-identified patient data collected between Jan 2014 and Dec 2021 from HSCT recipients, with refractory/resistant CMV or intolerance (RRI) to anti-CMV agents, from 14 transplant centers in France, Germany, Italy, Spain, UK, and US. This analysis focused on patients whose first CMV episode was considered intolerant to anti-CMV treatment and excluded patients whose first CMV episode was considered resistant or refractory to anti-CMV treatment. Patients may have had non-RRI episodes prior to and/or subsequent CMV episodes (including RRI) after their first intolerant episode. Data on CMV treatment patterns, clinical outcomes, and HCRU were collected and analyzed descriptively. Eighty-six (median age: 57 years; male: 56%) of 250 patients enrolled in the study experienced their first intolerant CMV episode. These 86 patients had a total of 160 CMV episodes during the study (Table). Valganciclovir was most frequently used at intolerance identification and for all CMV episodes (44% and 79% respectively), followed by foscarnet (31% and 66%), and ganciclovir (13% and 56%). For all CMV episodes, 83% (71/86) of patients received ≥2 therapies. Most patients (98%) had ≥1 anti-CMV therapy dose changes due to viremia resolved, lower maintenance dose, inadequate response and adverse events, most commonly with valganciclovir (75%), foscarnet (58%), and ganciclovir (49%). Intolerance was due to myelosuppression in 51% (most commonly neutropenia [73%; Table]) and nephrotoxicity in 33% of patients. All-cause mortality was 51%, and mortality 1-year post-intolerance identification was 47% (median follow-up from first intolerant CMV episode: 438 days). A total of 65 (76%) patients achieved viremia clearance during their first intolerant CMV episode (determined by the site investigator; Table). Fifty-five patients experienced ≥1 graft versus host disease events classed as acute, chronic, or severe in 49, 15, and 7 patients respectively. Over one-third (38%) experienced ≥1 CMV-related hospitalization. These results highlight the high burden of CMV infection for HSCT recipients who develop intolerance (primarily neutropenia) to available anti-CMV agents. In addition to patients being at risk of adverse outcomes, including mortality, a notable proportion failed to achieve viral clearance and/or experienced recurrence. There is a need for therapies that achieve and maintain CMV clearance with improved safety profiles.