The AFCRPLITY score for predicting the prognosis of immunotherapy combined with local-regional therapy in unresectable hepatocellular carcinoma

Background: Immunotherapy combined with intra-arterial therapy (IAT) has shown great potential in the treatment of unresectable hepatocellular carcinoma (uHCC). However, there are currently no available biomarkers that can predict the prognosis of immune-based combined therapy. Objectives: To establish a scoring method to predict prognosis in uHCC patients undergoing IAT plus immunotherapy. Methods: Between March 2019 and August 2022, uHCC patients undergoing IAT in combination with programmed cell death (ligand) 1 (PD-1)/PD-L1-based immunotherapy were retrospectively analyzed. Results: Among 1046 patients included, 780 patients were enrolled into hepatic arterial infusion chemotherapy immunotherapy cohorts (training set: n = 546, one center; external testing set: n = 234, three centers) and 266 patients were treated with trans-arterial chemoembolization (TACE) plus immunotherapy were enrolled into TACE immunotherapy cohort (validation set: n = 266). We developed the easy-to-apply alpha-fetoprotein (AFP), C-reactive protein (CRP), and platelet-to-lymphocyte ratio (PLR) in immunotherapy (AFCRPLITY) score and investigated the prognostic value of baseline variables on the disease control rate (DCR) and progression-free survival (PFS). HCC patients with low AFCRPLITY scores would have better PFS and DCRs than patients with high AFCRPLITY scores (AFCRPLITY 0: vs AFCRPLITY 1: vs AFCRPLITY 2: vs AFCRPLITY 3: p < 0.001 for PFS, p = 0.001 for DCRs) in the training set, which was confirmed in the external testing set and validation set. The highest level of CD8+ T cells was in the AFCRPLITY score = 0 group than the other two groups. Conclusion: The AFCRPLITY score is associated with PFS and DCR in uHCC patients receiving IATs plus immunotherapy. This score may be helpful for counseling, but prospective validation is needed. Design: A retrospective, multi-institutional study. Trial registration: The study has been retrospectively registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/, ChiCTR2300075828).