Real-life experience in two cases of secondary prophylaxis with letermovir for CMV infection in solid organ transplantation

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Abstract
The use of valganciclovir as secondary prophylaxis for cytomegalovirus (CMV) infection in solid organ transplantation (SOT) is the most prevalent therapeutic choice, but it has been dismissed by the presence of resistance and toxicity. Letermovir (LMV) is indicated as primary prophylaxis in hematopoietic stem cell transplantation, but there is scarce clinical data on its use as secondary prophylaxis in SOT. We present two cases of SOT recipients (lung, liver) who underwent LMV secondary prophylaxis. One patient developed the L595S ( UL97 )-resistant mutation to ganciclovir/valganciclovir and experienced several CMV relapses under LMV therapy, but no LMV resistance mutations were detected. The second patient developed the C325F ( UL56 )-resistant mutation to LMV under secondary prophylaxis which was rescued by foscarnet. This observation reviews previously published clinical data on LMV secondary prophylaxis and recommends a cautious use of LMV in the clinical practice due to the early development of UL56 resistance mutations. IMPORTANCE: This observation provides comprehensive data on the clinical correlates of both cytomegalovirus (CMV) genotypic follow-up and clinical monitoring and outcomes for two different solid organ transplantation recipients that received letermovir as secondary prophylaxis. Our study emphasizes that monitoring of CMV disease in the patient and early genotypic detection of resistance mutations are essential when using new antiviral drugs for off-label indication in patients experiencing CMV relapses or not responding to standard antiviral therapy. These cases and the bibliography reviewed can be helpful for other researchers and clinicians working in the field to optimize the use of new treatments for transplant recipients since drug-resistant CMV infection is an important emerging problem even with new developments in antiviral treatment.

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