Serum LAG-3 is associated with improved patient prognosis in high grade serous ovarian cancer (203)

Abstract

<b>Objectives:</b> With a five-year survival rate of only 39%, high-grade serous ovarian cancer (HGSOC) is the deadliest gynecologic cancer and a fifth leading cause of cancer-related deaths in women. Prior research has demonstrated a poor response to PD-1 based immunotherapy, despite the fact that ovarian tumors are considered immunogenic, highlighting a need to identify novel prognostic and therapeutic immunologic factors. Our prior data demonstrated intratumoral levels of immune co-inhibitory receptor LAG-3 as a marker of improved survival in HGSOC patients. In this study, we sought to evaluate the prognostic utility of serum-based LAG-3 and determine the variation in circulating LAG-3 levels in response to standard chemotherapy. <b>Methods:</b> Serum samples from patients with HGSOC were obtained from the Department of Special Testing and the Program in Women's Oncology Gynecologic Tissue Bank at Women and Infants Hospital. A total of 43 HGSOC treatment naïve serum samples were tested for serum LAG-3 and PD-1. In 20 of these patients, samples during and post- frontline platinum-based chemotherapy were analyzed. A commercially available ELISA kit was employed to detect serum LAG-3 and PD-1. This study was approved by the Women and Infants Institutional Review Board. <b>Results:</b> Pre-, on- and post-serum LAG-3 levels following frontline chemotherapy were not significantly changed. The median levels of LAG-3 decreased with the initiation of therapy, which persisted post-treatment. Kaplan-Meier curves analysis demonstrated longer progression-free survival (PFS) in patients with higher pre-treatment LAG-3 concentrations stratified by both median (HR: 0.4916, logrank p=0.022) and quartile (HR: 0.2679, log-rank p=0.0031) (Figure 1). In comparison, higher pre-treatment serum PD-1 levels were only found to be statistically significantly associated with an improved PFS when stratified by quartile (HR: 0.3894, log-rank p=0.0299) (Figure 1). Finally, upon stratification of patients by chemoresistant versus chemosensitive disease, it was revealed that patients with a PFS of six months or less had a significantly (p=0.0031) lower mean rank of pre-treatment serum LAG-3 when compared to patients with a PFS of 18 months or greater. <b>Conclusions:</b> These findings demonstrate that circulating immune checkpoint receptors have prognostic capabilities in HGSOC. Furthermore, our data suggest that circulating LAG-3 is an improved marker of prognosis compared to PD-1. Future directions include expanding upon our initial cohort size to validate these results.