Single‐center experience with use of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients

Abstract

Background: Cytomegalovirus (CMV) infection is common in thoracic organ transplant recipients. Valganciclovir and ganciclovir are used for both prophylaxis and treatment of this infection, but intolerance and treatment failure are common.Letermovir has been demonstrated to reduce the risk of CMV infection when used for prophylaxis in allogeneic hematopoietic cell transplantation. However, there are no data on its efficacy in thoracic organ transplantation. Methods:We examined the use of letermovir for either CMV prophylaxis (primary and secondary) or treatment in heart and lung transplant recipients at our institution from February 1, 2018, through December 31, 2018. Results: Nine total patients received letermovir at our institution (8 lung transplant, 1 heart transplant) during the study period. Letermovir was prescribed for CMV prophylaxis in eight patients (primary prophylaxis in two patients and secondary prophylaxis in 6 patients), and for treatment of CMV DNAemia in two cases. One patient received letermovir for both secondary prophylaxis and treatment on separate occasions. Three out of 8 (37.5%) patients receiving letermovir for prophylaxis developed CMV DNAemia during prophylaxis. One patient treated for CMV disease had clinical failure with a sharp rise in serum CMV DNA PCR. The other patient treated for lowgrade CMV DNAemia initially had a slight rise in CMV DNA PCR, but has since had a sustained response. No major side effects were experienced, and 2 patients reported minor side effects. Conclusion: Letermovir was well tolerated with only minor side effects reported; however, the rate of development of CMV DNAemia on prophylaxis was considerable. Further study of the dosing and efficacy of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients is warranted. K E Y W O R D S cytomegalovirus, heart transplantation, letermovir, lung transplantation 2 of 6 | ARYAL et AL. 1 | INTRODUC TI ON Cytomegalovirus (CMV) infection is a common complication among thoracic organ transplant recipients and often results in increased morbidity and mortality. 1 Ganciclovir and its prodrug, valganciclovir, are used for antiviral prophylaxis after thoracic organ transplantation in recipients with moderate or high risk of CMV infection. They are also the first-line drugs used in the treatment of CMV infection, and both share the same mechanism of action through inhibition of viral DNA polymerase. While these medications are effective, their use is limited by adverse effects and the risk for development of antiviral resistance. It is estimated that 7%-35% of thoracic organ transplant recipients develop leukopenia with 3%-15% of them affected by neutropenia, which can be associated with an increased risk of infection and death. 2 The hematologic complications of valganciclovir/ganciclovir therapy are often compounded by concomitant medication use in transplant recipients. Moreover, therapeutic failure may occur due to the development of resistance mediated by mutations in the genes UL97 and UL54. 3...

Suppression of CMV Infection with Letermovir in a Kidney Transplant Patient

“…A major difficulty is monitoring treatment response to letermovir, because DNA production by the infected cells continues, although shedding of infectious virus is prevented. Additionally, the delay until CMV DNA loads decline under treatment with letermovir may be considerable [ 5 ] . Unfortunately, pp65 antigenemia was also reported as an unreliable indicator of response to letermovir treatment in a case series of patients with drug-resistant CMV retinitis after solid organ transplantation [ 6 ] .…”

Letermovir and its role in the prevention of cytomegalovirus infection in seropositive patients receiving an allogeneic hematopoietic cell transplant

“…46 A single-center review of letermovir use in nine thoracic organ transplant recipients reported mixed results for both the prophylaxis and treatment of CMV disease (eight patients received letermovir for prophylaxis and two for treatment). 47 Of the eight patients who received letermovir prophylaxis (two primary and six secondary), three developed CMV DNAemia and were considered treatment failures. Of note, most of these patients were considered to be at high risk for CMV infection because of CMV mismatches (donor+/recipient-) or a history of CMV infection in those receiving letermovir as secondary prophylaxis.…”

“…Of note, most of these patients were considered to be at high risk for CMV infection because of CMV mismatches (donor+/recipient-) or a history of CMV infection in those receiving letermovir as secondary prophylaxis. 47 Letermovir treatment in solid organ transplant recipients At present, letermovir is not recommended for the treatment of CMV infection in HCT or solid organ transplant recipients; limited data exist for this treatment off label. In one of the first reported uses of letermovir for the treatment of CMV infections, compassionate use was initiated for multi-drug-resistant CMV disease in a lung transplant recipient.…”

Potential Therapeutic Approaches Against Brain Diseases Associated with Cytomegalovirus Infections

“…The drug was tested in CMV infected patients and may be useful for other patients who had organ transplantation or human immunodeficient virus (HIV) infections [63]. It has been clinically applied for CMV prophylaxis or treatment in hematopoietic stem cell recipients, thoracic organ recipients and lung transplantation recipients [64][65][66]. Letermovir has several advantages over conventional CMV antiviral agents such as administration orally, mild toxicity without myelotoxicity and nephrotoxicity [67,68], and targeting of the CMV terminase complex instead of CMV DNA polymerase without the possibility of cross-resistance with existing anti-CMV drugs [68].…”