Abstract 371: A single-center retrospective review assessing the use of tumor mutation burden as a predictor of therapeutic success in patients receiving immunotherapy

Background Cancer is a genetic disease in which cells may accumulate somatic mutations. The measurement of the frequency these somatic mutations occur is referred to as tumor mutational burden or TMB. A minority of these mutations may give rise to neoantigens that could in turn be recognized and targeted by the immune system. The more somatic mutations a tumor develops, the more likely these neoantigens are to form. Recent studies, namely KEYNOTE-158, found high TMB status to be associated with improved outcomes in patients receiving pembrolizumab monotherapy. Materials and Methods This was a single-center retrospective study that analyzed 73 patients who received cancer treatment at Avera Cancer Institute between June 2016 and July 2019. Patients were included/excluded from the final analysis based on having received at least one dose of pembrolizumab, ipilimumab, and/or nivolumab. Information was collected on patient characteristics, treatment, and clinical outcomes. The primary outcomes were complete and partial response rates and were assessed objectively based on a composite of radiographic reports, physician documentation, and treatment course. Secondary outcomes were clinical outcomes in patients with PD-1 and/or PD-L1 expression, clinical outcomes in patients receiving mono-immunotherapy vs combination therapy, and clinical outcomes based on the line of treatment in which immunotherapy was utilized. Results A total of 34 patients met the inclusion criteria of having a high TMB value (10 mutations/megabase) and having received one dose of pembrolizumab, ipilimumab, or nivolumab. Primary Outcomes•16 patients experienced a partial response (AR = 0.47) and 6 of these patients experienced a complete response (AR = 0.17) Secondary Outcomes•Absolute risk with prior TMB information (PR 0.43, CR: 0.17)•Absolute risks for monotherapy (PR: 0.375, CR: 0.125) vs combination therapy (PR: 0.556, CR: 0.375)•Average line of treatment for TF, PR, and CR were 2.24, 2, and 1.83 respectively. Discussion Studies like KEYNOTE-158 found a significant correlation between high TMB and improved clinical outcomes in patients receiving checkpoint inhibitors. However, in this cohort of patients high TMB status was not a good predictor of therapeutic success compared to the data presented in KEYNOTE-001, CHECKMATE-057, OAK, or PACIFIC. While there are limitations associated with the sample size, the data support that checkpoint therapy benefits patients when it is used earlier i