Background – Cancer immunotherapies provide durable benefits for many, but not all patients with various types of solid tumor. Accumulating research suggests that patients with ARID gene alterations of the human switch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex are more likely to respond to anti-PD-1/ PD-L1 and anti-CTLA-4 immunotherapy. To investigate the correlation between ARID gene alterations/RNA expression levels and clinical outcomes after immunotherapies, we reviewed patients with solid malignancies seen at our Institute.

Methods – A review of patients (from 2014 to 2024) with solid malignancies from our clinical database at the Avera Cancer Institute, whose tissue DNA and RNA were analyzed by next generation sequencing (NGS) by Tempus and Foundation Medicine, Inc. Patients who have alterations in the ARID gene (ARID1A, ARID1B, ARID2 and ARID5B) and received therapeutic regimens with immune checkpoint inhibitors (ICIs, including PD-1/PD-L1 and CTLA-4 inhibitors) alone or in combination with other treatments were assembled as Cohort 1. Patients with wild-type ARID gene and received ICIs were used as Cohort 2. The outcome differences of the patients between Cohort 1 and 2 were then assessed. Furthermore, patients in Cohort 1 were stratified to subgroups by RNA levels, microsatellite instability (MSI), as well as tumor mutational burden (TMB) status, and the outcomes were analyzed.

Results – 1. Of the 3620 patients in our database, we found 591 (16.3%) patients harboring ARID gene alterations with one of 15 types of cancer. This includes 160 (4.4% of 3620 and 27.1% of 591 patients) patients (Cohort 1) that received ICIs (excluding 10 patients unevaluable due to treatment termination per drug toxicity or lack of follow-up information), and 470 (13.0%) patients (Cohort 2) with wild-type ARID gene received ICIs. 2. No statistical difference of RNA expression level between Cohort 1 (N= 50) and Cohort 2 (N= 135). 3. Patients in Cohort 1 (N= 160), the median progression-free survival (PFS) and overall survival (OS) measured from date of the initiation of ICIs were 8.3 and 20.3 months. 4. PFS and OS of patients in Cohort 2 appear less than in Cohort 1. Assessment for patients of Cohort 2 and subgroups is ongoing. Updated results will be presented at the meeting.

Conclusion – Improved response rates to ICIs will require the efforts of researchers and clinicians to advance our understanding of tumor immunology, biology as well as omics and to integrate them with other important components of precision oncology. Our single-center observations of real-world data provide a reference for the clinical correlation between ARID gene alterations /RNA expression levels of the SWI/SNF complex and treatment outcomes after immunotherapy in malignant solid tumors, these findings might be beneficial for cancer patients’ treatment in the future.

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