Lifileucel produces confirmed responses in 2 of 3 treated adolescents with ICI-refractory metastatic melanoma

Lifileucel is an autologous tumor-infiltrating lymphocyte (TIL) therapy (adult US accelerated approval) given after cyclophosphamide/fludarabine lymphodepletion and followed by up to six doses of high-dose IL-2; here it was tested in a multicenter Phase I pediatric/adolescent melanoma cohort (NCT06566092) in immune checkpoint inhibitor-refractory metastatic melanoma. Five patients enrolled (median age 15; range 14–17); TIL manufacturing succeeded in 4/5, and 3/5 ultimately received lifileucel (one died of rapid progression pre-infusion). Among treated patients, 2/3 achieved confirmed partial responses by RECIST v1.1 (confirmed ORR 67%), while 1/3 had radiographic PD but symptomatic improvement with pleural effusion resolution. Grade 3–4 toxicities were largely lymphodepletion/IL-2 expected (notably cytopenias, hypotension/hypoxia/fever; plus atrial thrombosis and depressed level of consciousness in single patients), with a delayed thrombotic microangiopathy causing dialysis-dependent renal failure ~16 weeks post-infusion (treated with eculizumab; patient later died ~10 months post-TIL, cause unknown); no LD/IL-2-related deaths were reported.