Abstract A114: Impact of liver metastases and systemic biomarkers on immunotherapy response and survival outcomes in patients with solid tumors
Authors: Stephen Bettzy , Kwiatkowski Evan , Anderson Marcus R , Derbala Mohamed H , Salih Israa , Castillo Lilibeth , Yang Yali , Gurses Serdar A , Lim Joann T , Klekers Albert R , Le Hung , Kang Lei , Xu Mingxuan , Ahmed Jibran , Tan Harold N , Champiat Stephane , Tang Tin-Yun , Dumbrava Ecaterina E , Fu Siqing , Piha-Paul Sarina A , Ahnert Jordi Rodon , Tsimberidou Apostolia M , Yap Timothy , Yuan Ying , Hong David S , Meric-Bernstam Funda , Priya Bhosale , Naing Aung 
Published: February 2025

Background: As not all patients respond to immunotherapy, it is important to identify patients who are likely to benefit from treatment. Several factors such as hypoalbuminemia, elevated neutrophil counts, and increased LDH have been associated with poor response to immunotherapy and reduced survival outcomes. Similarly, liver metastases are associated with poor response to immune checkpoint inhibitors and survival in patients with melanoma and non-small cell lung cancer. However, its impact across all solid tumors and the effect of the location, number, and size of liver metastases on treatment outcomes is unknown. We therefore evaluated 595 patients with solid tumors treated on immunotherapy-based clinical trials in the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center between March 2016 and February 2022. Methods: Clinical, radiological, and laboratory data of the 595 patients were collected by review of their electronic medical records after obtaining informed consent. Using baseline CT images, based on the lobes involved, number, and size of liver metastases, we categorized liver metastases as mild, moderate, and severe. Responders were patients who had complete or partial response, or stable disease ≥6 months per RECISTv1.1. Overall survival (OS) was defined as time interval between treatment initiation and death was estimated using Kaplan-Meier method and compared by log-rank test. Results: Majority of the patients were female, white, ECOG of 1, had either gynecologic or gastrointestinal cancer. Of 595 patients, 470 were evaluable for response, 186 had liver metastases while 284 had no liver metastasis. Albumin level &lt;3.5 gm/dL (p=0.018), neutrophils &gt;7.3 K/uL (p=0.005), LDH &gt;225 U/L (p&lt;0.001) were associated with non-response, while lymphocyte count &gt;1.0 K/uL was associated with improved response (p=0.004). Similarly, median OS was significantly lower in patients with albumin level &lt;3.5 gm/dL (P&lt;0.001), neutrophils &gt;7.3 K/uL (p=0.003), LDH &gt;225 U/L (p=0.002), while it was higher in patients with lymphocyte count &gt;1.0 K/uL (p= 0.001). Non-response was significantly associated with liver metastases (46.4% vs 26.8%, p &lt;0.001). Stratified by response status, similar rates were observed in mild/moderate vs severe metastases groups (22.2% vs 24.2% non-responders; 14.6% vs 12.2% responders, pairwise p=0.54). The median OS was significantly lower in patients with liver metastases (6.51 months) vs those without (12.75 months; p&lt;0.001). The median OS was also significantly lower in patients with ascites (5.62 months) vs those without (10.28 months; p&lt;0.001) and in patients with liver metastases and ascites (5.62 months) vs those without (9.72 months; p=0.003). Conclusion: Patients with liver metastasis, regardless of severity of disease, have significantly poor response to immunotherapy and OS. This hypothesis generating finding suggest that initiating immunotherapy prior to the development of liver metastases could lead to better treatment outcomes. If validated, this approach could be practice changing.

Citation Format: Bettzy Stephen, Evan Kwiatkowski, Marcus R Anderson, Mohamed H Derbala, Israa Salih, Lilibeth Castillo, Yali Yang, Serdar A Gurses, Joann T Lim, Albert R Klekers, Hung Le, Lei Kang, Mingxuan Xu, Jibran Ahmed, Harold N Tan, Stephane Champiat, Tin-Yun Tang, Ecaterina E Dumbrava, Siqing Fu, Sarina A Piha-Paul, Jordi Rodon Ahnert, Apostolia M Tsimberidou, Timothy Yap, Ying Yuan, David S Hong, Funda Meric-Bernstam, Bhosale Priya, Aung Naing. Impact of liver metastases and systemic biomarkers on immunotherapy response and survival outcomes in patients with solid tumors [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A114.