226P - LongiBloodImmunoM: A multi-step analysis pipeline for longitudinal blood-based immunomonitoring for immunotherapy clinical trial

Background

Yttrium-90 (Y90)-resin microspheres radioembolization followed by nivolumab (Nivo) has shown encouraging response rate in advanced hepatocellular carcinoma (HCC), but only a subset of patients benefit from it. Predictive biomarkers help to identify patients for the treatment.

Methods

Longitudinal plasma and peripheral blood mononuclear cells (PBMCs) collection from HCC patients who received sequential Y90-RE followed by nivolumab (CA209-678; NCT03033446) allowed assessment of dynamics changes. Predictor selection procedure includes individual timepoint comparison, average analysis, trajectory description, responsiveness prediction, and combined modalities validation. 65-plex Human ProcartaPlex Luminex panel was employed to examine the concentration of cytokines and chemokines in 187 plasma samples collected at eight timepoints (responder [R]=11, non-responder [NR]=22). Immunomonitoring of PBMCs (NR=12, R=5) was assessed with a 39-plex Cytek panel followed by dimension reduction analysis. CXCL9 was reported impacting the immune treatment response, thus we focused on CXCL9+ CD8 cluster. Mixed models were fitted for responsiveness represented by Luminex analytes and CD8 phenotypes. Logistic regression and Cox model were fitted for the association between analytes and treatment response and 3-year overall survival (OS). Biomarkers showed significant association (P<0.05) and AUC > 0.7 were selected as the potential predictors.

Results

All Luminex biomarkers showed difference between the R and NR groups 14 days after Y90 treatment (P<0.05). The higher increment of IL-18, IL-12p70, and CCL24 after Y90 treatment related to better treatment response and 3-year OS. CXCL9+ and CXCR3+ CD8 clusters differed between R and NR on the 21^st and 35^th day after Y90-RE, respectively. IL-18 and IL-12p70 were significantly associated with CXCL9+ and CXCR3+ CD8 clusters in the Rs, but not NRs.

Conclusions

IL-18, IL-12p70, and CCL24 were potential predictors for treatment response as well as 3-year OS for HCC patients treated by Y90-Nivo.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.