MMDA-28 INTRACRANIAL AND EXTRACRANIAL PROGRESSION PATTERNS FOLLOWING TUMOR-INFILTRATING LYMPHOCYTE THERAPY IN METASTATIC MELANOMA: A SINGLE-CENTER EXPERIENCE

Abstract

Tumor-infiltrating lymphocyte (TIL) is an emerging treatment for metastatic melanoma following progression on immunotherapy and/or targeted therapy. However, patients with brain metastases (BM) remain underrepresented in studies and intracranial outcomes are poorly defined. We conducted a retrospective analysis of melanoma patients treated with TIL from April 2024 to April 2026 at NYP/Weill Cornell (n = 20). Patients with treated BM at the time of TIL and those who developed BM following therapy were identified. Clinical characteristics, including histologic subtype and mutation status, were collected. Intracranial and extracranial responses and progression patterns were assessed. The cohort included cutaneous (n = 10), acral (n = 4), and mucosal (n = 6) melanoma patients, with BRAF mutations in 5 patients and KIT mutations in 4 patients. The overall response rate (ORR) was 57%. At the time of TIL, 4 patients (20%) had BM, of whom 3 (75%) experienced intracranial progression. Among 16 patients without BM at baseline, 3 (19%) developed new BM following TIL. Across patients with CNS involvement (n = 7), intracranial progression preceded or coincided with systemic progression in the majority of cases (∼85%). Notably, discordance between intracranial and extracranial disease control was observed, including cases of initial extracranial response followed by CNS progression. Despite a high systemic response rate, TIL therapy was associated with frequent intracranial progression in patients with baseline CNS involvement. Discordant intracranial and extracranial responses suggest that the CNS may represent a site of relative resistance and an early indicator of systemic treatment failure. These findings highlight the need for improved strategies to optimize CNS disease control in patients receiving TIL therapy. Analyses of larger samples of patients with BM treated with TIL are necessary to better understand the pathophysiology of BM with respect to TIL.