The Use of Cytomegalovirus Cell Mediated Immunity to Optimize the Duration of Letermovir Prophylaxis in Hematopoietic Cell Transplant Recipients

Primary Objective

•To compare the proportion of CS-CMVi in allo-HCT recipients who had interrupted letermovir prophylaxis based on CMV CMI or extended duration of letermovir prophylaxis up to 200 days post transplantation.

Secondary Objectives

• To compare the proportion of CS-CMVi in HCT recipients who had interrupted letermovir prophylaxis based on CMV CMI or extended duration of letermovir prophylaxis at 365 days post transplantation.
• To compare the overall use of letermovir in HCT recipients in both arms.
• To compare CMV CMI in HCT recipients in both arms.
• To compare all-cause mortality and nonrelapse mortality between the 2 arms at day +200 and day +365.
• Healthcare expenditures for letermovir use and TCIP for both arms from day +100 to day +200.

Inclusion criteria

• Allogeneic HCT recipients with positive CMV serostatus
• On letermovir prophylaxis at day 90 post transplant (+/- 7 days)
• At high risk for CMV reactivation after day +100:

• Prior or active graft versus host disease requiring systemic steroids
• Mismatch stem cell donor (includes haploidentical, mismatch unrelated donor (MMUD), match related donor with at least one mismatch at one of the three specified HLA gene loci (HLA-A, HLA-B, or HLA-DR) and cord donor recipients)
• Received T cell depletion or anti thymoglobulin during conditioning
• CMV reactivation prior to day 100 post transplant
• On steroids at any dose within 2 weeks of enrollment

Exclusion criteria

• Patients under the age of 18
• Patients are discharged from our institution and unwilling to come back for follow up
• Patients are actively undergoing treatment for CS-CMVi at time of screening. Prior CS-CMVi is not an exclusion from study.
• Patients are allergic or intolerant to letermovir or have history of letermovir resistant CMV infection.
• Not able to procure letermovir for extended prophylaxis beyond day +100.