KRESLADI

Clinical summary

Indications and usage KRESLADI is indicated for the treatment of pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I) due to biallelic variants in ITGB2 without an available human leukocyte antigen (HLA)-matched sibling donor for allogeneic hematopoietic stem cell transplant. This indication is approved under accelerated approval based on increase in neutrophil CD18 and CD11a surface expression [see Clinical Studies (14) ]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Standard dosing For autologous use only. For intravenous use only. Patients must undergo hematopoietic stem cell (HSC) mobilization followed by apheresis to obtain CD34+ cells for KRESLADI manufacturing. ( 2.2 ) Dosing of KRESLADI is based on the number of CD34+ cells in the infusion bag(s) per kg of body weight. ( 2.1 ) The minimum recommended dose is 2.8 × 10 6 CD34+ cells/kg. ( 2.1 ) Full myeloablative conditioning must be administered before infusion of KRESLADI. ( 2.2 ) Verify the patient's identity matches the unique patient identification information on the KRESLADI infusion bag(s) prior to infusion. ( 2.2 ) Do not sample, alter, or irradiate KRESLADI. ( 2.2 ) Do not use an in-line blood filter or infusion pump. ( 2.3 ) Dose forms and strengths 6100000 1 MARNETEGRAGENE AUTOTEMCEL Contraindications None. Key warnings Serious Infections: Monitor patients for signs and symptoms of infection before and after KRESLADI infusion and treat appropriately. Administer prophylactic antimicrobials according to institutional guidelines. ( 5.1 ) Veno-Occlusive Disease: Monitor patients for signs and symptoms of veno-occlusive disease including assessment of liver function tests during the first month following KRESLADI infusion. ( 5.2 ) Neutrophil Engraftment Failure: Monitor absolute neutrophil counts (ANC) after KRESLADI infusion. If neutrophil engraftment does not occur administer rescue cells. ( 5.3 ) Delayed Platelet Engraftment: Monitor patients for thrombocytopenia and bleeding until platelet engraftment and count recovery. ( 5.4 ) LVV-mediated Insertional Oncogenesis: Monitor patients at least annually for hematologic malignancies for at least 15 years after KRESLADI infusion. ( 5.5 ) Hypersensitivity Reactions: Monitor for hypersensitivity reactions during the infusion. ( 5.6 ) Drug interactions No formal drug interaction studies have been performed. KRESLADI is not expected to interact with the hepatic cytochrome P-450 family of enzymes or drug transporters. Pregnancy guidance Risk Summary There are no available data from KRESLADI administration in pregnant women. No animal reproductive and developmental toxicity studies have been conducted to assess whether KRESLADI can cause fetal harm when administered to a pregnant woman. No nonclinical germline transmission studies have been conducted with KRESLADI. KRESLADI must not be administered during pregnancy because of the risk associated with conditioning. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.