Dr Moschos on Treatment Strategies With Adoptive T-Cell Therapy in Melanoma

"Bridging therapy is a means to reduce the tumor burden to a level that [makes] the effect of the cellular therapy greater. [Cellular therapy] is a dangerous path for someone with uncontrolled growth of their tumor…[therefore,] it is essential that the moment that you identify the patient going [to receive] adoptive T-cell therapy, [you] identify a bridging therapy."

Stergios J. Moschos, MD, an associate professor of medicine in the Department of Medicine in the Division of Oncology at the University of North Carolina (UNC) Chapel Hill School of Medicine, UNC Health, emphasized the importance of appropriately administering bridging therapy to patients who are slated to receive the adoptive T-cell therapy lifileucel (Amtagvi).

Patient selection plays a critical role in the successful administration of adoptive T-cell therapies, Moschos began. One key determinant of successful treatment is the use of effective bridging therapy to reduce tumor burden prior to lymphodepletion and cell infusion, Moschos stated. The rationale behind bridging therapy is to achieve disease control and minimize tumor burden, thereby enhancing the efficacy of cellular therapy and reducing the risk of treatment-related toxicities, he explained.

Patients with rapidly progressive disease or a high tumor burden are at elevated risk for severe toxicity during lymphodepleting chemotherapy, which may compromise their ability to receive or benefit from subsequent cell therapy, Moschos stated. Therefore, early identification of appropriate bridging strategies is essential once a patient is deemed a candidate for cellular therapy, he reiterated. Therapeutic agents used during this period may include a MEK inhibitor, a PD-1 inhibitor, or lenvatinib (Lenvima), Moschos outlined.

Notably, the combination of lenvatinib and pembrolizumab (Keytruda) has demonstrated a median duration of response of approximately 9 months in various tumor types, Moschos reported. This extended response window can provide oncologists with valuable time to lower disease burden and optimize the patient’s overall condition prior to proceeding with lifileucel, he stated. Ultimately, careful sequencing of therapies, including the timely integration of bridging regimens, can significantly influence outcomes and should be considered a fundamental component of cellular therapy planning, Moschos concluded.