Wilson-Miller, Justine

Background/Objectives: Tumor-infiltrating lymphocyte (TIL) therapy is an important option for patients with metastatic melanoma progressing after standard systemic therapy, but real-world data on treatment delivery, toxicity monitoring, and immune recovery remain limited. We evaluated clinical outcomes, treatment tolerance, immune reconstitution, and cardiac biomarker dynamics across three Mayo Clinic sites. Methods: We retrospectively analyzed adults with metastatic melanoma who received lymphodepleting chemotherapy followed by TIL infusion and high-dose interleukin-2 (IL-2) between April 2024 and December 2025. Clinical outcomes, treatment delivery, and adverse events were assessed. Longitudinal immune monitoring included CD4 and CD8 T-cell counts, CD4:CD8 ratio, and immunoglobulin G (IgG) at baseline and follow-up. In a prespecified cardiac sub-cohort, high-sensitivity troponin (hs-Tn) was measured during IL-2 administration to evaluate associations with cardiac events and IL-2 interruption. Results: Thirty-six patients underwent TIL infusion. The objective response rate was 50.0%, including complete responses in 13.9%, and the disease control rate was 72.2%. Median progression-free survival was 3.61 months, and median overall survival was 12.94 months. M1d disease was associated with inferior overall survival on univariable analysis (HR 6.55, 95% CI 2.03–21.17; p = 0.002), with attenuation after multivariable adjustment. Receipt of ≥3 IL-2 doses was associated with longer overall survival on univariable analysis (HR 0.20, 95% CI 0.06–0.64; p = 0.007), but this association also attenuated after adjustment. Longitudinal immune monitoring demonstrated persistent CD4 lymphopenia through 6 months, sustained inversion of the CD4:CD8 ratio, and declining IgG at months 3 and 6. In the cardiac sub-cohort (24 patients; 87 IL-2 doses), post-dose hs-Tn ≥15 ng/L was associated with clinically significant cardiac events (OR 9.6, 95% CI 1.5–60.6; p = 0.016) and IL-2 interruption (OR 3.4, 95% CI 1.1–10.7; p = 0.036). For cardiac events, hs-Tn ≥15 ng/L had 100% sensitivity and 100% negative predictive value. Conclusions: In routine practice, TIL therapy was feasible and active in metastatic melanoma. M1d disease identified a subgroup with poor survival, peri-dose hs-Tn showed promise as a tool to support safer IL-2 delivery, and prolonged CD4 suppression with IgG decline suggests that recovery after TIL therapy extends beyond initial hematologic reconstitution. These findings support prospective validation of biomarker-guided IL-2 monitoring and extended post-treatment immune surveillance.

9557 Background: High-dose interleukin-2 (IL-2) is administered following tumor-infiltrating lymphocyte (TIL) therapy, yet cardiotoxicity frequently limits dose delivery. The clinical significance of peri-dose troponin elevations during IL-2 remains poorly defined. We evaluated troponin kinetics during IL-2 dosing and their association with significant cardiac events and IL-2 interruption. Methods: We retrospectively analyzed patients with metastatic melanoma treated with TIL therapy followed by inpatient high-dose IL-2 at Mayo Clinic Rochester (N = 24; 87 IL-2 doses). High-sensitivity troponin and ECGs were obtained before and after each IL-2 dose. Clinically significant cardiac events were defined as QTc prolongation > 480 ms, arrhythmias (excluding isolated sinus tachycardia), new ECG abnormalities, vasopressor requirement, or cardiology consultation. Dose-level outcomes included cardiac events and subsequent IL-2 dose interruption. Paired troponin changes were assessed using Wilcoxon signed-rank testing. Dose-level associations were evaluated using clustered logistic regression to account for repeated IL-2 doses within patients. Results: 24 patients received 87 IL-2 doses (median 3 [IQR 2 - 5]). Median age was 63 years (IQR 54 - 70), and 58% were male. Baseline troponin median was 11 ng/L (IQR 6 - 21); 38% had baseline troponin > 14 ng/L. Post-dose troponin exceeded 14 ng/L in 16/24 patients (67%) and 48/87 doses (52%). Median delta troponin was 0 ng/L (IQR −1 to 6; range −24 to 133), with post-dose levels higher than pre-dose values ( p = 0.02). Clinically significant cardiac events occurred in 33% of patients; no post-IL-2 reductions in left ventricular ejection fraction were observed. At the dose level, cardiac events occurred only when post-dose troponin exceeded 14 ng/L (15/48 [31%] vs 0/39 doses; p < 0.001). In clustered logistic regression, post-dose troponin ≥15 ng/L was independently associated with cardiac events (OR 9.6, 95% CI 1.5 - 60.6; p = 0.02) and subsequent IL-2 dose interruption (OR 3.4, 95% CI 1.1 - 10.7; p = 0.04). When modeled continuously, each 1-unit increase in log-transformed post-dose troponin was associated with higher odds of cardiac events (OR 3.3, 95% CI 1.6 - 6.7; p = 0.001) and IL-2 interruption (OR 2.8, 95% CI 1.6 - 4.9; p < 0.001). Baseline troponin correlated with peak post-dose troponin (ρ = 0.44, p = 0.04). Conclusions: Peri-dose troponin elevations are common during post-TIL high-dose IL-2; however, higher post-dose troponin independently identifies clinically significant cardiac toxicity and predicts IL-2 interruption after accounting for repeated dosing within patients. Baseline troponin modestly predicts peak elevations, supporting standardized, risk-stratified troponin monitoring and prospective evaluation of toxicity-adaptive IL-2 delivery strategies in TIL therapy.