Preliminary Outcomes of Letermovir Use for Cytomegalovirus Prophylaxis: A Retrospective Assessment at a Single Center

Abstract

Introduction Cytomegalovirus (CMV) is associated with significant morbidity and mortality in the hematopoietic cell transplant (HCT) population. In the absence of prophylaxis, reactivation occurs in upwards of 80% of seropositive allogeneic HCT recipients and primary infections in roughly 15% of CMV-mismatched HCTs. Agents used to prevent clinically significant CMV (csCMV) including ganciclovir and foscarnet can be associated with toxicities including renal dysfunction and myelosuppression. Letermovir is a novel antiviral targeting the viral terminase complex and has demonstrated efficacy in preventing csCMV in adult CMV seropositive allogeneic HCT recipients with minimal associated toxicities. Objectives To describe a single center experience of the use of letermovir as primary and secondary prophylaxis in adult allogeneic HCT recipients. Methods This retrospective analysis assessed 25 adult HCT patients receiving letermovir for primary or secondary prophylaxis between January 1, 2018 and September 24, 2018. Primary prophylaxis per hospital protocol was given through approximately d+100 in CMV seropositive recipients and also allowed in CMV seronegative recipients with seropositive donors. csCMV was defined as CMV viremia necessitating preemptive therapy or CMV disease. Patients were evaluated for development of csCMV on letermovir prophylaxis, early cessation of prophylaxis due to perceived toxicities, and development of csCMV post-cessation of primary prophylaxis. Results Twenty-two patients received letermovir for primary CMV prophylaxis. The primary underlying disease was AML (7/22, 32%). CMV serostatus was as follows: D-/R+ (9/22, 41%), D+/R+ (9/22, 41%), D+/R- (4/22, 18%). Letermovir was initiated ata median of 5.5 days post-transplant. Median letermovir duration was 95 days post-transplant. Early cessation due to perceived toxicities occurred in 41% (7/22) of patients. Reasons for early discontinuation were ongoing cytopenias (4/7, 44%) and nausea (3/7, 33%). No csCMV developed during therapy. In patients completing the intended primary prophylaxis (n = 10), thus far no patients have developed csCMV within a median duration of 150 days post letermovir cessation. Three patients received letermovir for secondary prophylaxis. All were CMV seropositive and high risk on basis of haploidentical donors (2/3, 67%) and use of cord blood (1/3, 33%). Therapy was initiated a median of 57 days post-transplant with no patients developing csCMV on therapy. Conclusions Letermovir was an effective antiviral in both primary and secondary CMV prophylaxis and was generally well tolerated. Side effects directly related to letermovir were difficult to assess in this complex patient population. Close monitoring is required following cessation of primary prophylaxis. Prospective studies defining the optimal duration for letermovir prophylaxis are needed.