Dimou, A.

e21521 Background: Outcomes following tumor-infiltrating lymphocyte (TIL) therapy vary in real-world practice, and accessible predictors are needed to inform patient selection and timing of referral. We evaluated whether baseline disease burden, metastatic distribution, and treatment delivery factors are associated with outcomes following TIL therapy. Methods: We retrospectively analyzed patients with metastatic melanoma treated with TIL therapy across Mayo Clinic sites (N = 27 infused). Baseline disease burden was characterized using AJCC metastatic stage and organ-specific involvement. A composite high visceral burden variable was defined as the presence of M1d disease and/or liver metastases. Bridging therapy use prior to infusion was recorded. Post-infusion IL-2 exposure was categorized as low (0-2 doses) vs. high (3-6 doses). Best overall response (BOR) was summarized using RECIST-based standard criteria. Overall survival (OS) and progression-free survival (PFS) were measured from TIL infusion and estimated using Kaplan–Meier methods with univariable Cox regression. Results: Median age at infusion was 62.0 years; 59.3% were male. Melanoma subtypes included cutaneous (81.5%) and mucosal (18.5%). Bridging therapy was used in 48.1%. Baseline metastatic stage was M1a/M1b in 18.5%, M1c in 63.0%, and M1d in 18.5%. Median follow up was 8.3 months. BOR included complete response (18.5%), partial response (37.0%), stable disease (22.2%), and progressive disease (22.2%), yielding an objective response rate of 55.6% and disease control rate of 77.8%. Patients with high visceral disease burden experienced inferior OS vs. those without high visceral burden (median 5.2 vs 13.4 months; HR 4.77, 95% CI 1.22–18.63; p = 0.014). Bridging therapy was not associated with OS or PFS. Higher post-infusion IL-2 exposure (seen in 77.8% of patients) was associated with improved OS (median 9.0 vs 3.7 months; HR 0.16, 95% CI 0.04–0.67, p = 0.005), likely reflecting early post-infusion clinical tolerance rather than a causal treatment effect. Median PFS for the cohort was 3.6 months and did not differ by IL-2 exposure ( p = 0.3), metastatic stage ( p = 0.8), bridging therapy ( p = 0.7), liver metastases ( p = 0.2), or LDH above upper limit of normal ( p = 0.1). Conclusions: The above findings are hypothesis generating and will support evaluation in larger cohort. In this real-world cohort of patients treated with TIL therapy, baseline visceral disease burden was strongly associated with survival outcomes, while bridging therapy did not compromise post-infusion efficacy among patients proceeding to infusion. Post-infusion IL-2 exposure correlated with OS and likely reflects early treatment tolerance. These readily available clinical features may inform patient counseling, referral timing, and sequencing decisions as TIL therapy enters broader clinical use.

Abstract Background: High-dose interleukin-2 (IL-2) is administered after tumor-infiltrating lymphocyte (TIL) infusion to promote in-vivo expansion and persistence, yet optimal dosing and the clinical significance of out-of-specification (OOS) TIL products remain unclear. We investigated the impact of number of infused IL-2 doses and manufacturing OOS status on outcomes in metastatic melanoma treated with commercial TIL therapy. Methods: We retrospectively analyzed 31 patients treated across three Mayo Clinic sites. Planned IL-2 was 600,000 IU/kg every 12 hours for ≤6 doses; actual dosing varied based on clinical tolerance. Patients were grouped as low (0-2) vs high (≥3) IL-2 doses. TIL products were classified as within-specification or OOS per commercial release criteria. Survival associations were evaluated using Kaplan-Meier and multivariable Cox regression. Results: In our 31-patient cohort, the median age was 59 years (range 17-77), 58% were male, and 84% had ECOG 0. At TIL infusion, M-stage distribution was M1a 6%, M1b 10%, M1c 61%, and M1d 23%. LDH was elevated above the upper limit of normal in 42%. The median number of IL-2 infusions was 4 (range 0-6); 58% of patients received ≥3 doses, while 2 patients (6%) received none. Out-of-specification (OOS) TIL products occurred in 6 patients (19%). Best responses included complete response (26%) and partial response (23%), for an overall response rate of 48% and a disease-control rate of 61% (CR + PR + SD). Among responders, the median duration of response was 84 days (95% CI 73-95). At data cutoff, the median follow-up was 253 days (95% CI 137-370). The most common grade 3/4 toxicities occurring >14 days after TIL infusion were lymphopenia (39%), anemia (16%), and thrombocytopenia (10%). Median progression-free survival (PFS) was 99 days (95% CI 73-125) with 20 progression events, and median overall survival (OS) was 193 days (95% CI 32-354) with 13 deaths. Number of infused IL-2 doses was dependent on patients tolerability. Receiving ≥3 IL-2 doses was associated with improved overall survival (394 vs 101 days; p < 0.001) and a trend toward longer progression-free survival (110 vs 59 days; p = 0.055). OOS products predicted inferior PFS (30 vs 110 days; p = 0.003) and showed a trend toward worse OS (120 vs 394 days; p = 0.079). In multivariate analysis, ≥3 IL-2 doses independently improved PFS (HR 0.20, 95% CI 0.06-0.69; p = 0.011) and OS (HR 0.09, 0.02-0.36; p = 0.001), while OOS status increased risk of progression (HR 8.10, 2.24-29.25; p = 0.001) and death (HR 6.16, 1.35-28.20; p = 0.019). Conclusions: Higher number of infused doses IL-2 and meeting commercial TIL release criteria were independently associated with improved outcomes. Citation Format: Mohamed A. Aboelatta, Jeffrey E. Johnson, Jabra G. Zarka, Matyáš Benada, James W. Jakub, Roxana S. Dronca, Ruqin Chen, Mahesh Seetharam, Deepti Behl, Svetomir N. Markovic, Lisa A. Kottschade, Heather N. Montane, Matthew S. Block, Anastasios Dimou, Robert R. McWilliams, Paula Gill, Yi Lin, Arkadiusz Z. Dudek. Impact of number of IL-2 infusions and product out of specification status on outcomes of tumor infiltrating lymphocyte therapy for melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3706.

Abstract Background: Tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager (TCE) is FDA approved in patients (pts) with extensive stage small cell lung cancer (ES-SCLC), after progression on frontline chemoimmunotherapy. We aimed to evaluate the immune cell profile in pts who received this therapy in standard-of-care (SOC) practice with progression free survival (PFS) less than and greater than two months (mo). Methods: Patients who received tarlatamab at Mayo Clinic Rochester and consented to immuno phenotyping of blood are included in the present study. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Microsoft Excel and PRISM. Results: Eighteen patients with median age 64 (range 37-79) were included in the study. 66% of our cohort were women and 83% had present or past history of smoking, with an average of 40 pack years (range 26-60). With a median follow-up of 2 months, the median PFS for the cohort was 1.5 mo (range 0.33-2.76 months). 61% (13/18) of patients had PFS <2mo. 39% (5/18) had PFS>2mo and of which, three patients had partial response with one maintaining stable disease and one patient with mixed response. At baseline (BL), there were no difference in T cell, CD4 or CD8 cell count between patients in the PFS<2mo and PFS>2mo groups. Patients with PFS<2mo had higher exhausted CD8 T cells compared to those in the PFS>2mo group (CD8+PD1+TIGIT+CD57+, PFS<3mo vs >3mo, cells/mL: 7.14±4.28, 1.58±1.37, p=0.009). Additionally, when analyzing the B-cell population, the PFS<2mo group had lower percentage of B cells compared to the group with PFS>2mo at baseline (6.0±7.5, 10.4±14, p=0.02). At day 7, the group with PFS<2mo had lower Treg compared to the group with PFS>2mo (2.88±1.38, 4.60±1.47, p=0.02). Also, the PFS<2mo group had an increase of B cells compared to the group with PFS>2mo at day 7(<2mo vs >2mo: 10.0±14, 4.37±3.07, p=0.04). Finally, the group with PFS>2mo had decrease in total monocytes (mono), classical mono, and immunosuppressive cells (PFS<2mo vs >2mo, Mono: 340±347, 253±106, p=0.04. Classical mono: 305±283, 155±109, p=0.02. CD14+HLA-DRneg: 105.8±96, 12±39, p=0.03) compared to the group with PFS<2mo by day 7. While no changes were seen between BL and day 7 for intermediate mono in PFS<2mo group, PFS>2mo group had decreased post treatment intermediate monocytes (BL vs day 7, cells/mL, intermed mono: 32.5±15,17.7±6.2, p=0.03). Conclusion: In this study investigating the SOC outcomes of tarlatamab, early progression was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at AACR meeting. Citation Format: Dhauna Karam Prasad, Andre De Menezes Silva Corraes, Malvika Gupta, Audrey Ma, Chen Wu, Zuoyi Shao, Kevin Reagan, Rayaan Kamal, Ashley Potter, Abdullah Al-Ajmi, Syeda Mina, Sykler J. Taylor, Antonious Hazim, Anastasios Dimou, Kaushal Parikh, Mohammed Shanshal, Ailsa Luce, Anna Schwecke, Julian Molina, Aaron Mansfield, Katherine Smith, Lucy Holmes, Haidong Dong, Yi Lin, Konstantinos Leventakos. Immune cell profile changes in patients treated with tarlatamab for extensive stage small cell lung cancer in real world practice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3931.