CMV-Specific T Cell Immunity (CMV-TCIP) Directed Letermovir to Prevent CMV Infection in Patients Who Received Donor Stem Cell Transplantation

PRIMARY OBJECTIVE:

I. To prospectively evaluate the efficacy of Viracor cytomegalovirus (CMV) specific T cell immunity panel (CMV-TCIP)-directed letermovir prophylaxis in preventing clinically significant CMV infection (CS-CMVi) in CMV-seropositive recipients of allogeneic hematopoietic stem cell transplantation (AHCT) or AHCT recipients using a stem cell graft from a CMV-serology positive donor.

SECONDARY OBJECTIVES:

I. To prospectively evaluate the efficacy of Viracor CMV-TCIP-directed letermovir prophylaxis in preventing CMV disease in CMV-seropositive recipients or AHCT recipients using a stem cell graft from a CMV-serology positive donor.

II. To determine cost-effectiveness of CMV-TCIP-directed letermovir prophylaxis in comparison with the conventional fixed-duration approach in CMV-seropositive recipients of AHCT or AHCT recipients using a stem cell graft from a CMV serology positive donor.

III. To determine the performance of CMV-TCIP assay in predicting immunoprotective effect against subsequent CS-CMVi in CMV-seropositive recipients of AHCT or AHCT recipients using a stem cell graft from a CMV serology positive donor.

EXPLORATORY OBJECTIVES:

I. To study patterns of CMV-specific immune reconstitution within 1-year posttransplant using sequential CMV-TCIP assays in CMV-seropositive recipients of AHCT or AHCT recipients using a stem cell graft from a CMV-serology positive donor.

II. To determine adverse events of letermovir for CMV prophylaxis.

III. To determine the incidence of CMV drug resistance in AHCT recipients receiving Viracor CMV-TCIP-directed letermovir prophylaxis.

IV. To determine quality of life (QoL) of patients treated with Viracor CMV-TCIP-directed letermovir prophylaxis.

OUTLINE:

Patients receive letermovir intravenously (IV) and switched to orally (PO) when tolerated once per day (QD) for up to 52 weeks in the absence of unacceptable toxicity. Starting at 28 weeks, patients undergo blood sample collection monthly for CMV TCIP testing, and stop taking letermovir if they receive a positive test result for two consecutive occasions, 1 month apart, indicating CMV immunity. Patients with a positive result at 28 and 32 weeks undergo blood sample collection for CMV TCIP testing again at 52 weeks. Patients with positive CMV-TCIP test who received significant immunosuppression repeat the CMV-TCIP test at 1 week after initiating treatment and, if negative, resume letermovir PO or IV QD with monthly CMV-TCIP testing until receiving a positive result for two consecutive occasions, 1 month apart (up to 52 weeks). Patients with CS-CMVi discontinue letermovir. Patients with positive CMV-TCIP testing who develop CS-CMVi receive CMV-directed therapy. Following treatment for CS-CMVi, patients may resume letermovir at the discretion of the treating physician, CMV-TCIP testing is discontinued, and patients are followed up for the remainder of the 52 weeks.