3135 - Prediction of PACIFIC Regimen Efficacy by Measuring Serum Autoantibody Response Against Cancer Antigens Using the MUSCAT Assay

05:00pm - 06:00pm PT

Hall F

Screen: 13

POSTER

Presenter(s)

Masanori Someya, MD, PhD - Sapporo Medical University, Sapporo, Hokkaido

M. Someya¹, M. Kitagawa², T. Hasegawa², T. Mori³, T. Honjo³, A. Miyamoto³, T. Tsuchiya², T. Gocho², and J. Futami³; ¹Department of Radiology, Sapporo Medical University, Sapporo, Japan, ²Department of Radiology, School of Medicine, Sapporo Medical University, Sapporo, Japan, ³Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan

Purpose/Objective(s): We examined temporal changes in serum autoantibodies to cancer antigens in patients receiving chemoradiotherapy (CRT) and maintenance therapy with immune checkpoint inhibitor (ICI) for unresectable non-small cell lung cancer to predict response to treatment.

Materials/Methods: Twenty patients who underwent 60 Gy in 30 fractions of CRT followed by Durvalmab from July 2020 to October 2023 were included. Blood samples were collected at three time points: before treatment, at the end of CRT, and 2 weeks after the first ICI administration, and 130 types of autoantibodies against cancer antigens in serum was measured using the MUSCAT (multiple S-cationized antigenimmobilized bead array) assay. The antibody titers at the end of CRT and 2 weeks after the first ICI were compared, and a 2-fold or greater increase was defined as a spark response, and an increase up to 1.5-fold as an incremental response. We also examined the percentage of PD-L1 expression in tumor samples.

Results: The median follow-up time was 23 months (11 - 52 months), with 9 cases of Complete response (CR) and 11 cases of Progressive disease (PD). Spark response of autoantibodies was observed in 7 cases, PD-L1 expression was <1% in 4 cases, 1-49% in 10 cases, and >50% in 6 cases. Five of the seven patients with a spark response had CR, and all seven patients with autoantibodies (MAEL or KRT8) incremental response experienced PD. A risk score was calculated by combining three factors: Spark response, PD-L1 >50%, and incremental response of MAEL or KRT8, dividing patients into low-risk and high-risk groups. The 2-year PFS was 85.7% in the low-risk group and 11.1% in the high-risk group, with a statistically significant difference (p<0.01).

Discussion: After CRT with ICI, humoral immunity mediated by B cells was found to be activated in some cases. Changes in autoantibody titers against cancer antigens were observed, and those cases that showed favorable immune responses such as spark responses tended to be associated with favorable treatment outcomes. Whereas, progressive responses of autoantibodies such as MAEL or KRT8 were associated with poor response to treatment, suggesting that it might be a predictive marker for recurrence. A risk score combining these immune responses with PD-L1 expression may be useful for prediction for CRT+ICI.

Conclusion: Although the number of cases is limited, measurement of autoantibodies against cancer antigens by the MUSCAT assay may be a useful for predicting response to CRT+ICI.