Cytomegalovirus End-Organ Disease after Allogenic Hematopoietic Cell Transplant: Descriptive and Comparative Analysis in the Era of Letermovir Prophylaxis

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Background Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic cell transplantation (HCT) is common and associated with increased morbidity and mortality. Letermovir (LTV) primary prophylaxis for high-risk patients has markedly reduced CMV reactivation post-transplant and improved outcomes. However, outcomes of patients diagnosed with CMV end organ disease (EOD) and its incidence in the era of LTV primary prophylaxis are unknown. Objectives To compare the clinical outcomes of CMV EOD among HCT recipients with or without LTV primary prophylaxis. Methods We conducted a single-center retrospective cohort study that included HCT recipients between March 2016 and December 2022 who developed CMVEOD within 48 weeks post-transplant; only patients who were recipient CMV seropositive were included. Outcomes of interest were sites of CMV EOD, time from HCT to CMV EOD, and all-cause (ACM) and non-relapse mortality (NRM) at 48 weeks. We performed Fisher’s exact tests and Mann–Whitney U tests for comparison as appropriate. Results Among 1,941 CMV seropositive HCT recipients, CMV EOD occurred in 80 patients (4%); 27 (2%) and 53 (9%) occurred in HCT recipients with or without LTV primary prophylaxis respectively. HCT recipients on LTV prophylaxis were more often male and underwent transplant in later years, reflecting the timing of LTV FDA approval (Table 1). Most HCT recipients had lung (63%) and gastrointestinal (GI) (24%) involvement of CMV; 9% of patients had multiple CMV sites. When compared to patients not on LTV prophylaxis, most HCT recipients on LTV developed late CMV EOD past 100 days post-transplant (Table 2). LTV breakthrough occurred in 10 of 27 patients (37%); of those only 5 had UL56 genotype testing, but no resistance mutations were detected. ACM and NRM at 24 and 48 weeks were lower in HCT recipients on LTV but were not statistically significant (Table 2). ACM at 48 weeks was highest in patients with EOD of the lungs compared to other EOD sites in patients with or without LTV (Figure 1). Conclusion HCT recipients are still at risk for CMV EOD although the incidence decreased with LTV primary prophylaxis. Across all EOD cases, mortality was significantly higher in patients with pneumonitis compared to GI disease. HCT patients who received LTV for primary prophylaxis had more often CMV EOD after day 100 post-transplant but with trends towards lower ACM and NRM at 24 or 48 weeks post-transplant.

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