Dr Olson on Toxicities Associated With Lifileucel and IL-2 in Melanoma

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.

Although patients may experience transient AEs during lifileucel treatment, the therapy's one-time administration offers the advantage of temporary toxicity, he continues. Typically, high-grade toxicities resolve within 2 to 3 weeks post-treatment, allowing a return to baseline health status as blood counts recover, according to Olson. Patient selection for lifileucel therapy hinges significantly on patients’ ability to tolerate IL-2, given its intense nature and potential exacerbation of underlying comorbidities, such as cardiac, pulmonary, or renal issues, Olson says.

Consequently, careful consideration of patient health status, including cardiac stress testing and overall fitness, is paramount to ensure appropriate candidacy for lifileucel therapy, Olson emphasizes. Although temporary, lifileucel-associated AEs necessitate thorough evaluation of patient suitability and close monitoring to optimize treatment outcomes, he concludes.