Radt-42. Nascent Clinical Experience With Radiotherapeutic Management of Melanoma Brain Metastases in Patients Treated With Tumor-Infiltrating Lymphocyte (Til) Therapy

Tumor-infiltrating lymphocyte (TIL) therapy is an emerging treatment option for treatment-refractory melanoma. TIL therapy involves tumor harvest, isolation and ex vivo expansion of TILs, followed by lymphodepletion prior to infusion. TIL therapy studies excluded patients with uncontrolled melanoma brain metastases (MBMs), partially due to concerns about intralesional hemorrhage. While radiation therapy (RT) is a cornerstone of MBM management, there are limited data on RT safety and efficacy during the peri-TIL timeframe. We performed a retrospective analysis of patients with advanced melanoma that underwent TIL harvest at a single institution from March 2024 to April 2025, with medical records reviewed for clinical outcomes and adverse events. Of 40 patients who underwent TIL harvest, 27.5% (n=11) had MBMs and were stratified by timing of MBMs in relation to TIL harvest and receipt of RT. Of patients with MBMs, 55% harbored a BRAF V600E variant, median time from TIL harvest to infusion was 2.0 months, and median follow-up post-harvest was 5.9 months, 36% (4 of 11 patients) had known MBMs and underwent RT >2mo prior to TIL harvest, 45% developed new MBMs between TIL harvest and infusion, 73% (8 of 11 patients) underwent RT, 7 of whom were treated with focal stereotactic RT. Of note, 50% of patients that underwent RT had evidence of possible intralesional bleed noted on brain MRI prior to RT. RT-related toxicity was minimal with no cases of radiation necrosis, new/worsening intracranial bleeding, or grade 3+ toxicities. Neurotoxicity related to TIL therapy included grade 2-3 encephalopathy, grade 3 fatigue, and grade 2 headaches. At last follow-up, regional brain control was 64% and irradiated local control was 88%. Our institutional experience suggests that MBMs in patients undergoing TIL therapy are not uncommon, and RT is a safe and feasible option for ‘bridging’ therapy for intracranial disease control.