Conversion therapy using transarterial chemoembolization plus tislelizumab for unresectable hepatocellular carcinoma:...

We analyzed the clinical efficacy and safety of conversion therapy for unresectable hepatocellular carcinoma (uHCC) using transarterial chemoembolization (TACE) plus tislelizumab and characterized its effects on the tumor and immune landscape.

Fifty-seven patients with uHCC undergoing TACE plus tislelizumab from March 2020 to October 2024 were potentially eligible, and thirty-two patients finally enrolled. The efficacy endpoints included successful conversion rate, objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Treatment-related adverse events (TRAEs) were recorded according to CTCAE v5.0. Hematoxylin and eosin (HE) staining was used to evaluate tumor necrosis and lymphocyte infiltration. Immunohistochemistry (IHC) was performed to differentiate tumor immune infiltrates via a set of markers.

The best overall responses were 9.4% CR, 46.9% PR, 37.5% SD, and 6.3% PD, the ORR was 56.3%. Better ORR was shown in patients with AFP ≥ 400 ng/mL or tumor number < 3. The median PFS and OS was 13.9 (95% CI 2.6-25.2) and 29.2 (95% CI 13.7-44.7) months, respectively. Thirty-two patients (100%) experienced TRAEs of any grade, eight patients (25%) experienced grade 3/4 TRAEs. Fifteen patients (46.9%) with uHCC successfully converted. Notably, HE staining revealed extensive tumor necrosis and massive infiltration of lymphocytes in HCC and at the tumor-non-tumor interface in converted specimens. Further characterization by IHC revealed increased infiltration of CD8 + T and Th1 cells in the tumor of converted patients.

TACE plus tislelizumab may be a potent and safe conversion regimen for uHCC due to its ability to generate profound tumor necrosis and anti-tumor immune response.