Impact of CMV-Specific Immune Reconstitution at the End of Letermovir Prophylaxis on the Development of Late Cytomegalovirus Infection in Hematopoietic Stem Cell Transplant Recipients (INMUNOEND)

Impact of CMV-Specific Immune Reconstitution at the End of Letermovir Prophylaxis on the Development of Late Cytomegalovirus Infection in HSCT Recipients (INMUNOEND): a Protocol for a Prospective, Observational, Multicenter Study

Cytomegalovirus (CMV) infection is a common complication in patients undergoing hematopoietic stem cell transplantation (SCT). Fixed-duration letermovir (LTV) prophylaxis during the first 100 days post-SCT is effective and safe in preventing this infection, although it may be associated with a delay in CMV-specific immune reconstitution. Hence, it is needed a study to evaluate whether the absence of CMV-specific immune reconstitution at the end of LTV prophylaxis is associated with the development of late infection. This could facilitate the individualization of CMV prophylaxis duration in these patients.

Methods and analysis: INMUNOEND is a multicenter, prospective, observational, non-interventional study including CMV seropositive patients undergoing allo-SCT who receive LTV prophylaxis during the first 100 days post-SCT. Immunological and virological monitorization will be conducted until day +200 post-SCT. The primary outcome variable is the percentage of patients who develop clinically significant CMV infection up to day +200 post-SCT after completing LTV prophylaxis. Data collected will include: baseline characteristics of the hematological diseases and comorbidities, variables related to SCT (i.e. engrafment, graft-versus-host disease, use of letermovir and CMV replication) and variables related to CMV-specific immune reconstitution.

Inclusion Criteria:

• Age >18 years.
• CMV seropositivity (positive IgG) in the recipient at the time of SCT.
• First allogeneic hematopoietic stem cell transplant recipient (bone marrow, peripheral blood, or cord blood).
• Within the first 28 days post-SCT at the time of inclusion.
• Indication for LTV prophylaxis within the first 28 days post-transplant up to 100 days post-SCT, according to the criteria established in each center.

Exclusion Criteria:

• CMV seronegativity (negative IgG) in the recipient at the time of transplant.
• Previous allogeneic stem cell transplant (patients with a prior autologous transplant are allowed to be included).
• History of CMV disease in the 6 months prior to inclusion.
• Need for preemptive therapy in the month prior to inclusion in the study.
• Received any of the following in the 14 days prior to inclusion: Ganciclovir, valganciclovir, foscarnet, acyclovir (at doses >3200 mg orally per day or >25 mg/kg IV per day), valacyclovir (at doses >3000 mg orally per day), famciclovir (at doses >1500 mg orally per day).
• Received any of the following in the 30 days prior to screening: Cidofovir, CMV hyperimmune immunoglobulin, any CMV antiviral in the investigational phase.
• Suspected or confirmed hypersensitivity reaction to the LTV formulation or any of its components.
• Severe hepatic insufficiency (defined as Child-Pugh class C).
• History of primary immunodeficiency prior to transplant.
• Participation in a clinical trial involving the administration of CMV vaccines, other investigational CMV drugs, or monoclonal antibodies.