Letermovir(Prevymis™) Guidelines for Inpatient Use UCSF Medical Center P&T ID Sub-committee Meeting Presented by: Mimi Lo PharmD, BCPS, BCOP Hematology/Oncology Pharmacist

Letermovir (Prevymis™) Indication FDA labeled indication: Prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of allogeneic hematopoietic stem cell transplant (HSCT) Dosing Letermovir 480mg IV/PO once daily starting between day 0 – 28 post allo stem cell transplant (before or after engraftment) and continue through day 100 post transplantation. P&T Recommendation UCSF Medical Center formulary restricted to Adult Malignant Hematology (for prophylaxis indications), Pediatric Blood and Marrow Transplant (for prophylaxis indications) and Infectious Diseases (Adult & Pediatric, for all other indications)

Adult Allogeneic HSCT Letermovir Guidelines Letermovir therapy should be restricted to CMV seropositive recipients of: Haploidentical grafts, myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) Mismatched related or unrelated donor grafts, MAC or RIC Cord blood grafts, MAC or RIC T cell depleted (ie, CD34 selected) grafts, MAC or RIC Recipients of any graft type diagnosed with acute GVHD requiring >= 1mg/kg prednisone

Adult Allogeneic HSCT Letermovir Guidelines Letermovir will start upon discharge from the initial transplant hospitalization (~day +14-19) Patients in the high risk categories remaining hospitalized beyond day +20 will start letermovir inpatient Patients with aGVHD requiring prednisone >=1mg/kg, start letermovir within 3 days of starting prednisone even if inpatient and prior to day +20 For any patient with history of CMV reactivation prior to transplant, letermovir can be started sooner than day +20 at the discretion of the primary BMT provider.

Adult Allogeneic HSCT Letermovir Guidelines For all groups, letermovir should be continued until at least day +100 May consider longer duration therapy in those with impaired immune reconstitution — ie, those still on significant steroid doses (>20mg prednisone per day) at day +100 and/or those with CD4 counts <200 at day +100 and/or unable to taper immune suppression. The endpoint of letermovir therapy will be individualized for each patient at the discretion of the primary provider. For patients on letermovir as outpatients who are admitted to the hospital for non-CMV related indications, letermovir would be continued as an inpatient. Patients admitted for CMV disease would stop letermovir and start appropriate therapy with valganciclovir or ganciclovir and letermovir would not be restarted after CMV treatment is complete.

Pediatric Allogeneic HSCT Letermovir Guidelines Letermovir therapy should be restricted to CMV seropositive recipients of: Haploidentical grafts, myeloablative conditioning (MAC) or reduced intensity conditioning (RIC) Mismatched related or unrelated donor grafts, MAC or RIC Cord blood grafts, MAC or RIC T cell depleted (ie, CD34 selected) grafts, MAC or RIC Recipients of any graft type diagnosed with acute GVHD requiring >= 1mg/kg prednisone Restricted to patients ≥ 15 years old and weight > 35 kg

Pediatric Allogeneic HSCT Letermovir Guidelines Letermovir will start on Day +1 following allogeneic stem cell transplant For all groups, letermovir should be continued until at least day +100 May be switched to valganciclovir sooner at the discretion of the treating team if cell counts allow For patients on letermovir as outpatients who are admitted to the hospital for non-CMV related indications, letermovir would be continued as an inpatient Patients admitted for CMV disease would stop letermovir and start appropriate therapy with valganciclovir or ganciclovir and letermovir would not be restarted after CMV treatment is complete