Molecular characterization and treatment patterns of lung cancer in solid organ transplant (SOT) recipients.

e20699 Background: SOT recipients are at increased risk of malignancy due to immunosuppression. Lung cancer is among the most common post-transplant cancers, yet molecular characteristics and treatment patterns remain poorly defined. As targeted therapies shape non-small cell lung cancer (NSCLC) care, understanding tumor genomics is essential. Methods: We conducted a single-institution retrospective study of SOT recipients diagnosed with lung cancer 2007-2025. Demographic, transplant, histologic, molecular, treatment, and survival data were abstracted. Molecular analyses focused on NSCLC, including PD-L1 tumor proportion score (TPS) and next-generation sequencing (NGS). Overall survival (OS) was assessed by molecular and treatment subgroups. Results: 85 SOT recipients developed lung cancer (73 NSCLC - 43 adenocarcinoma [adenoCa], 30 squamous). Median age at diagnosis was 66 years, median time from transplant to diagnosis was 5.4 years, and median follow-up was 9 months. Lung was the most common transplanted organ (33%), followed by kidney (28%) and heart (22%). 53 NSCLC patients had TPS assessed, and 49 had NGS. TPS did not differ significantly by histology; most tumors had low TPS ( < 1%) (44% adenoCa vs 60% squamous), while intermediate TPS (10–50%) was more frequent in adenoCa (25% vs 15%). Actionable mutations were identified more often in adenoCa patients (42% vs 3%, p = 0.0001), most commonly KRAS G12C (15%) and classical EGFR mutations (14%). There was no significant difference in OS between patients with actionable versus non-actionable mutations (1-year OS 68% vs 52%). In contrast, OS differed significantly by treatment strategy (p < 0.0001), with 1-year OS of 50% for chemoimmunotherapy, 43% for targeted therapy and 14% for chemotherapy. Conclusions: NSCLC after SOT has a molecular landscape comparable to the general population, supporting comprehensive molecular profiling. However, TPS was lower and co-mutation patterns differed, suggesting immunosuppression may affect tumor biology. Despite frequent actionable mutations, survival was driven more by treatment strategy than molecular status, highlighting potential underuse of targeted approaches, low uptake of immunotherapy despite strategies to improve post-transplant safety, and the need for further study on transplant-specific tumor biology. Actionable mutations and systemic therapy patterns by stage of NSCLC. Characteristics Stage I (n=34) Stage II (n=7) Stage III (n=7) Stage IV (n=29) Total (n=77) p value N (%) N (%) N (%) N (%) N (%) Actionable Mutation 0.2 No 22 (64.7%) 6 (85.7%) 7 (100%) 23 (79.3%) 58 (75.3%) Yes 12 (35.3%) 1 (14.3%) 0 (0%) 6 (20.7%) 19 (24.7%) Systemic Therapy 0.0005 Chemotherapy 2 (5.9%) 3 (42.9%) 2 (28.6%) 16 (55.2%) 23 (29.9%) Chemoimmunotherapy 0 (0%) 0 (0%) 0 (0%) 2 (6.9%) 2 (2.6%) Targeted Therapy/Chemo 4 (11.8%) 1 (14.3%) 1 (14.3%) 7 (24.1%) 13 (16.9%) None 28 (82.4%) 3 (42.9%) 4 (57.1%) 4 (13.8%) 39 (50.6%)