Drug Interactions between lovotibeglogene autotemcel and sargramostim

GENERALLY AVOID: Colony-stimulating factors should generally be avoided in patients with sickle cell disease (SCD) who plan to undergo treatment with autologous hematopoietic stem cell (HSC)-based gene therapy (e.g., exagamglogene autotemcel, lovotibeglogene autotemcel). The exact mechanism has not been fully described but may relate to an increase in the production of leukocytes by the colony-stimulating factor. Available literature on patients with SCD has noted a positive correlation between high leukocyte counts and worse clinical outcomes (e.g., early death, silent brain infarct, hemorrhagic stroke, and acute chest syndrome). Leukocytes in SCD patients appear to be able to attach to erythrocytes and the vascular endothelium, resulting in vaso-occlusion. They may also heighten the inflammatory response when monocytes secrete inflammatory mediators (e.g., TNF-alpha, interleukin-1b). In addition, out of 11 individuals with SCD who received granulocyte-colony stimulating factor (G-CSF), 6 developed severe adverse reactions (e.g., vaso-occlusive crises (VOC), multiorgan failure) and 1 death was reported.

MANAGEMENT: Granulocyte-colony stimulating factor (G-CSF) is not recommended for CD34+ HSC mobilization, or in some cases at all, in sickle cell patients preparing for autologous HSC-based gene therapy. Additionally, the protocols for clinical studies in sickle cell patients who underwent treatment with exagamglogene autotemcel or lovotibeglogene autotemcel did not recommend the use of G-CSF within the first 21 days after receipt of the gene therapy infusion.