Mutational profile, clinical characterization, and outcomes of lung cancer in solid organ transplant recipients.

Abstract

e21131 Background: Solid organ transplant recipients have increased risk for malignancies. Lung cancer is the second most common malignancy in this population. Those patients are usually on long-term immunosuppressive medications that may affect tumorigenesis, cancer characteristics, and treatment response. Previous studies have investigated the characteristics and outcomes of post-transplant patients with lung cancer in small-sized cohorts. However, the tumor mutational profile and detailed treatment response at different stages have not been reported. Methods: We conducted a retrospective study from a cohort of 52 solid organ transplant recipients who were diagnosed with lung cancer at Mayo Clinic from 2018 to 2021. We examined tumor molecular alteration using next generation sequencing (NGS), analyzed the treatment modalities, progression-free survival (PFS), and overall survival (OS) and compared those to the general population with lung cancer using historical data in previous large trials. Results: In our study, most transplanted solid organs are kidney (N = 28, 53.8%), followed by liver (N = 12, 23.1%) and heart (N = 9, 17.3%). The adenocarcinoma (N = 28, 53.8%) represented the most common histology, followed by squamous cell carcinoma (N = 19, 36.5%). It consisted of Stage I (30.8%), stage II (15.4%), stage III (25%), and stage IV (26.9%). The most common site of metastasis is bone (64.3%). Transplant recipients with lung cancer have a significantly high frequency of somatic BRCA 1/2 mutations (30.4%), compared to the general population with advanced lung cancer (2.1%, p < 0.001). The frequencies of TP53 mutations (52.2%) and EGFR mutations (30.4%) are also increased. For stage I patients who received surgery or radiation therapy, the disease-free survival (DFS) is 16.5 months. 9 of 14 stage IV patients received chemotherapy. The median number of cycles received is 4. The median PFS is 4.9 months, and the median OS of all stage IV patients is 6.1 months. 4 patients were found to have actionable EGFR mutations, and 3 of them were initially diagnosed with stage IIIA and received Osimertinib after progression. One stage IV patient who was post-liver transplant received pembrolizumab for up to 5 cycles before he developed aspiration pneumonia and then pursued hospice. The PFS is 3.7 months. No immune-related adverse event was reported. Conclusions: In our cohort of solid organ transplant recipients who developed lung cancer, we observed a much higher frequency of somatic BRCA 1/2 mutations, compared to the general population with lung cancer. In addition, our data suggested post-transplant patients with stage I lung cancer have a shorter disease-free survival, and patients with stage IV lung cancer have a shorter overall survival, compared to the general population with lung cancer. Further study containing a high number of solid transplant patients to validate these findings is warranted.