Drug Interactions between exagamglogene autotemcel and hydroxyurea

GENERALLY AVOID: Hydroxyurea may affect the manufacturing and efficacy of the autologous genome edited hematopoietic stem cell (HSC)-based gene therapy, exagamglogene autotemcel. The exact mechanism has not been described, but could be related to hydroxyurea's ability to interfere with DNA synthesis and/or its bone marrow suppressive effects, potentially reducing the number of HSCs. HSC mobilization followed by apheresis is required to isolate the CD34+ cells needed for exagamglogene autotemcel production. Previous studies available in the medical literature have shown that hydroxyurea treatment is associated with a decreased level of CD34+ cells in both the peripheral blood and bone marrow. One study revealed that the number of peripheral blood CD34+ cells was 2.5 cells/microL of blood in hydroxyurea treated patients (n=31), 19 cells/microL in treatment naive patients (n=19) and those receiving chronic transfusions (n=19), and 7.3 cells/microL in the control group (individuals without sickle cell disease, n=25). Clinical data evaluating the use of hydroxyurea 8 weeks prior to the planned start of mobilization and conditioning as well as after the receipt of exagamglogene autotemcel are not available.

MANAGEMENT: The manufacturer of exagamglogene autotemcel recommends discontinuation of hydroxyurea at least 8 weeks prior to the start of each mobilization cycle and conditioning. Additionally, there is no experience with the use of hydroxyurea after a patient receives treatment with exagamglogene autotemcel.