MP56-02: The Effect of Tumor Mutational Burden, PDL1 Expression, and Somatic Gene Alterations on Advanced Bladder Cancer Response to Cisplatin Chemotherapy
Introduction: Cisplatin based chemotherapy is a mainstay of treatment for patients with advanced bladder cancer, however not all patients achieve clinical response. We sought to understand how tumor mutational burden (TMB), PDL1 expression, and somatic tumor alterations were associated with response to cisplatin therapy by utilizing the Tempus Lens platform, a web-based library of clinical and molecular data. Methods: We selected patients on the Lens platform, managed by Tempus (Chicago, Illinois), with stage 3 and 4 bladder cancer who received cisplatin chemotherapy. Somatic gene mutations via next-generation sequencing (NGS), TMB (> 10 mutations/Mb), and PDL1 expression on tumor and immune cells were assessed against rates of clinical response. Analyses were performed with chi-square test at significance of p = 0.05. Results: 5.4 million patients were assessed as part of the Lens platform. 4,049 patients with stage 3 or 4 bladder cancer were identified. Clinical response to cisplatin therapy and NGS data was available for 305. In this dataset, PDL1 expression on greater than 10% of tumor cells was associated with worse response to cisplatin therapy as 23% of patients with progressive disease (PD) had this finding compared to 6% of those with complete response (CR) (p= 0.046) (Table 1). Similarly, PDL1 expression on great than 10% of tumor infiltrating immune cells was lower in patients with CR compared to PR (0% vs 29%, p = 0.02). TMB appeared to be associated with improved response, with high TMP seen in 27% of patients with CR and 19% in patients with PD, although this difference was not significant (p = 0.14). Certain somatic alterations were associated with CR while others were associated with PD (Figure 1). Conclusions: While it is known that PDL1 expression is important in response to immunotherapy, our data suggest PDL1 expression by tumor and immune cells is also associated with response to cisplatin chemotherapy. Specific somatic alterations may be associated with response or lack of response to cisplatin as well. SOURCE OF Funding: none