2577 - Nascent Clinical Experience with Radiotherapeutic Management of Melanoma Brain Metastases in Patients Treated with Tumor-Infiltrating Lymphocyte (TIL) Therapy
Presenter(s)
A. Choudhury1, D. P. Lawrence2, M. J. Frigault3, S. Cohen2, M. J. Mooradian2, R. J. Sullivan2, M. J. Khandekar4, K. S. Oh5, P. Brastianos6, H. A. Shih7, A. M. Haugh2, and A. E. Marciscano8; 1Harvard Radiation Oncology Program, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Massachusetts General Hospital/ Harvard Medical School, Boston, MA, 4Harvard Medical School, Boston, MA, 5Harvard Medical Center, Boston, MA, 6Massachusetts General Hospital Cancer Center, Boston, MA, 7Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 8Department of Radiation Oncology, Mass General Brigham/ Massachusetts General Hospital, Boston, MA
Purpose/Objective(s): Tumor-infiltrating lymphocyte (TIL) therapy is an emerging treatment option for treatment-refractory melanoma, FDA-approved in 2024. TIL therapy involves tumor harvest, isolation and ex vivo expansion of TIL, followed by lymphodepletion prior to TIL infusion. Studies for TIL therapy approval excluded patients with uncontrolled melanoma brain metastases (MBMs). Given the timeline from TIL harvest to infusion and use of lymphodepletion there are concerns about intralesional hemorrhage, intracranial progression and radiation therapy (RT) toxicity. While RT remains a cornerstone in management of MBMs, there are limited data on management during the peri-TIL therapy window and the safety/efficacy of integrating RT. Herein we review our institutional experience on clinical outcomes and toxicity among patients undergoing RT for MBMs that underwent TIL harvest.
Materials/Methods: We performed a retrospective analysis of patients with advanced melanoma that underwent TIL harvest at a single institution from May to December 2024. Patients with MBMs were stratified by receipt of RT and timing of development of MBMs in relation to date of TIL harvest. Medical records were reviewed with attention to clinical outcomes, RT parameters and adverse events (CTCAEv5.0) related to TIL therapy or RT.
Results: A total of 9 patients with MBMs and undergoing TIL harvest were identified. Median age was 63.2 years, and 55% of patients harbored a BRAF V600E variant. Median time from TIL harvest to infusion was 2.1 months and median follow-up post-harvest was 4.4 (2.1-8.3) months. One patient did not undergo infusion due to TIL product not meeting specification. Two patients had known MBMs and underwent RT >3mo prior to TIL harvest. 55% (5 of 9) of patients developed new MBMs during the window from TIL harvest to infusion. 67% (6 of 9 patients) underwent brain-directed RT. 83% (5 of 6) were treated with focal stereotactic RT with 10 MBMs treated over 6 treatment courses. One patient underwent hippocampal-avoidant WBRT. 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 grade 1-2 fatigue, grade 1 headaches and no radiographic or symptomatic radiation necrosis. There were no intracranial bleeding events after TIL harvest. Neurotoxicity related to TIL therapy was observed including grade 2-3 encephalopathy, grade 3 fatigue, and grade 2 headaches. At last follow up, regional brain control was 67% and irradiated local control was 83%.
Conclusion: Our institutional experience suggests that treatment of MBMs with RT in patients undergoing TIL therapy is feasible and safe. Given the risk of intracranial progression or development of new MBMs between TIL harvest and infusion, RT is an option as a consolidative ‘bridging’ therapy for intracranial disease control.