Letermovir Treatment for Refractory or Resistant Cytomegalovirus Infection or Disease or with Concurrent Organ Dysfunction: A Phase 2 Open Label Study.

Introduction: Refractory or resistant cytomegalovirus (CMV) infection and disease pose a significant challenge in immunocompromised patients, including solid organ transplant (SOT) and allogeneic hematopoietic cell transplant (allo-HCT) recipients. This study aimed to evaluate letermovir as a treatment for patients with CMV infection or disease. Methods: We performed an open-label, phase II non-randomized clinical trial. Adult and paediatric (≥12 years of age) patients who had undergone an SOT or allo-HCT and who required antiviral treatment for refractory or resistant CMV or who had CMV with concurrent organ dysfunction were eligible. Patients received letermovir treatment daily for up to 12 weeks with an optional additional 12 weeks of therapy for secondary prophylaxis if clinically indicated. The primary objectives were to evaluate the safety and efficacy of letermovir treatment based upon virological and clinical responses. Results: Ten patients were enrolled in the study, and seven patients completed the study treatment and follow-up period. The overall virological response (defined as a complete virological response at the end of the study period) rate was 60% in the study population. The study drug was well tolerated, as only two patients experienced study drug-related toxicity and only one grade 3 toxicity (elevated ALT) was observed. Letermovir was not associated with acute kidney injury, hepatotoxicity, cardiac arrhythmias, or bone marrow suppression. Conclusion: In this limited sample, letermovir for CMV treatment was safe and well tolerated. Further research is needed to determine if letermovir can be used for the treatment of refractory or resistant CMV infection or disease.