Abstract LB429: Impact of severe liver metastases on clinical response to immunotherapy in solid tumors

Background: The presence of liver metastases negatively influences immunotherapy response across solid tumors by promoting an immunosuppressive microenvironment. However, it remains unclear whether a specific threshold of liver metastases, defined by lesion size and number, is associated with progressively worse response to immunotherapy-based regimens. Methods: We retrospectively analyzed clinical and radiologic data from 594 patients with advanced solid tumors treated on immunotherapy-based clinical trials at the University of Texas MD Anderson Cancer Center between 3/2016 and 2/2022 (IRB-approved protocol PA15-0315). Baseline imaging categorized liver metastases as 1) absent; 2) mild (<5 lesions, all <3 cm); 3) moderate (<5 lesions with ≥1 lesion ≥3 cm); or 4) severe (≥5 lesions of any size). Tumor response was assessed by RECIST v1.1. Responders were defined as complete response, partial response, or stable disease (SD) lasting ≥6 months; non-responders included SD <6 months, progressive disease, or clinical progression. Odds ratios (ORs) and 95% confidence intervals (CI) for response were estimated using logistic regression. Results: Of the 594 patients, 52% were female, 79% were white, 90% had an ECOG performance status of 1. The most common tumor types were gastrointestinal (18%) and gynecologic (14%) malignancies. A total of 537 were evaluable for response. Liver metastases were present in 213 (mild n=40, moderate n=34, severe n=139) and absent in 324 patients. The presence of liver metastases was significantly associated with lower response rates (p<0.001). Patients with severe liver metastases had lower odds of response compared to those with mild/moderate liver metastases, though the difference did not reach statistical significance (OR 0.69, 95% CI 0.30-1.58; p=0.39). The odds of response were significantly lower in patients with mild/moderate liver metastases than in patients without liver metastases (OR 0.46, 95% CI 0.23-0.90; p=0.024). Severe liver metastasis was associated with significantly lower odds of response compared to none or mild/moderate disease (OR 0.36, 95% CI 0.20-0.64; p=0.0004). Conclusions: The presence of liver metastases is associated with lower response rate to immunotherapy-based regimen. Patients with severe liver metastases demonstrated significantly lower odds of response compared to those with no or mild/moderate metastases. Therefore, severe liver metastases may represent a clinically meaningful threshold for worse response and may inform risk stratification and clinical trial eligibility. Citation Format: Jibran Ahmed, Bettzy Stephen, Evan Kwiatkowski, Marcus R. Anderson, Mohamed H. Derbala, Israa Salih, Lilibeth Castillo, Yali Yang, Serdar A. Gurses, Hao Yan, Joann T. Lim, Albert R. Klekers, Hung Le, Lei Kang, Mingxuan Xu, Harold N. Tan, Stephane Champiat, Tin-Yun Tang, Ecaterina E. Dumbrava, Sarina A. Piha-Paul, Jordi Rodon Ahnert, Apostolia M. Tsimberidou, Timothy A. Yap, Siqing Fu, David S. Hong, Funda Meric-Bernstam, Priya R. Bhosale, Aung Naing. Impact of severe liver metastases on clinical response to immunotherapy in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB429.