Dr Olson on Toxicities Associated With Lifileucel and IL-2 in Melanoma
Source: OncLive, April 2024
Daniel Olson, MD, assistant professor, medicine, the University of Chicago Medical Center, UChicago Medicine, discusses toxicities associated with lifileucel (Amtagvi) and interleukin-2 (IL-2)in patients with unresectable or metastatic melanoma.
Notably, in February 2024, lifileucel was granted FDA accelerated approval for the treatment of adult patients with previously treated unresectable or metastatic melanoma. The adverse effects (AEs) associated with the lifileucel-based regimen predominantly stem not from lifileucel itself but from the conditioning chemotherapy and IL-2 component, Olson begins. Lifileucel, which comprises a patient’s own T cells, does not inherently induce significant toxicity, as these cells are sensitized to self-antigens and typically do not provoke cross-reactions or cytokine release, contrasting with engineered cell therapies such as CAR T cells and T-cell receptor T cells. Consequently, the personalized nature of lifileucel immunotherapy minimizes off-target or off-tumor effects, he reports.
Lymphodepleting chemotherapy commonly leads to cytopenias due to a decline in blood cell counts, and IL-2 therapy is associated with its own set of toxicities, including fever, rash, hypotension, and thrombocytopenia, he reports. Despite prior use of IL-2 in higher doses for conditions such as melanoma and renal cell cancer, lifileucel therapy employs IL-2 primarily to activate patient T cells rather than to maximize dosing, aiming to mitigate serious AEs, such as vascular leak syndrome, Olson elucidates.