Lifileucel shows promise in metastatic-melanoma patients whose disease had progressed on standard immune-checkpoint inhibitors (ICI) and other therapies, according to a small open-label trial. "Lifileucel is a ground-breaking form of cellular immunotherapy that utilizes the immune cells of patients derived from their own tumors as a treatment," Dr. Amod A. Sarnaik of Moffitt Cancer Center, in Tampa, Florida, told Reuters Health by email. "The study results demonstrate relatively long-lasting responses in patients whose melanomas did not respond to initial treatments." Dr. Sarnaik and colleagues studied 66 patients with unresectable or metastatic melanoma. The patients had received a mean of more than three previous therapies, with 99% having progressed on prior anti-PD-1 or PD-L1 therapy, and 77% having done so on prior anti-CTLA-4 therapy. They were given a single infusion of lifileucel, followed by up to six infusions of high-dose interleukin-2 within 24 hours. The median time from lifileucel infusion to best response was 1.4 months, the authors report in the Journal of Clinical Oncology. There were two complete responses and 22 partial responses, giving an investigator-assessed objective response rate (ORR) of 36%. In addition, 44% showed stable disease and 81% of evaluable patients had a reduction in tumor burden. After a median study follow-up of 18.7-months, the median duration of response was not reached. In the 42 patients who were refractory to anti- PD-1 or PD-L1 therapy, the ORR was 41%. All patients experienced at least one treatment-emergent adverse events (TEAEs), with the most common grade-3 or -4 TEAEs including thrombocytopenia (82%), anemia (56%) and febrile neutropenia (55%). This safety profile, say the researchers, was consistent with known adverse events associated with non-myeloablative lymphodepletion and interleukin-2. "Based upon these findings," concluded Dr. Sarnaik, "the treatment is under consideration for (Food and Drugs Administration) approval and is being investigated in other forms of cancer. As a cancer specialist, I look forward to this class of treatment having a long-lasting impact on the lives of patients afflicted with advanced malignancies." Dr. Joseph J. Skitzki of Roswell Park Cancer Institute, in Buffalo, New York, who was not involved in the study, told Reuters Health by email that the publication "represents a milestone in the translation of cellular adoptive immunotherapy from the (National Institutes of Health) and other highly select academic sites to a more universal and standardized application." "Cellular adoptive immunotherapy has always represented an intriguing option for melanoma patients who have failed all other therapies as it can generate impressive responses, and now this study shows a potential clinical benefit in patients who have failed modern immunotherapy and small molecule therapy options," he added. Dr. Skitzki, an associate professor of oncology, cautioned, "While the study is groundbreaking in workflow to obtain tumor-infiltrating lymphocytes (TIL) from geographically distant patients and facilities and generate cellular products at a central source, it still suffers from some of the historic drawbacks of TIL immunotherapy, namely a selection bias of patients that are capable of generating a product, the concomitant use of (interleukin-2) and how this may have profound anti-tumor efficacy itself, and the concern for longevity of the infused product." "In this study," he added, "about 85% of patients were able to generate a TIL product, this is much higher than the historic rates seen at the (National Cancer Institute) and would be more than expected from the majority of patients with 'cold' melanoma tumors that lack TIL (i.e., this could be selection bias as the patients were on average 3 therapies into their treatment and may have been more likely to have TIL). Future studies would be helpful to determine if this high percentage rate of production from TIL is maintained and/or how the individual contributions of (interleukin-2) influenced the observed outcomes." Iovance Biotherapeutics, which developed lifileucel, designed and sponsored the trial. Dr. Sarnaik has financial ties to the company, and some of his coauthors are company employees. —David Douglas Source
