Addition of Dendritic Cell Vaccination to Conditioning Cyclophosphamide and Chemoembolization in Patients with Hepatocellular Carcinoma: The ImmunoTACE Trial.

PURPOSE

A previous study by our group using dendritic cells (DC) pulsed ex vivo with the lysate of the HepG2 cell line showed evidence of antigen-specific T-cell responses in some patients with advanced hepatocellular carcinoma. The ImmunoTACE trial evaluated the preliminary activity of this vaccine in combination with transarterial chemoembolization (TACE) in patients with intermediate-stage hepatocellular carcinoma.

PATIENTS AND METHODS

A randomized phase II trial was conducted in three tertiary referral centers in the United Kingdom. Eligible patients were randomly assigned in a 1:1 ratio to TACE + preconditioning cyclophosphamide or to TACE + preconditioning cyclophosphamide + DC infusions. The primary endpoint was progression-free survival time using RECIST v1.1 criteria. Additional endpoints included safety and immune responses.

RESULTS

Between March 2016 and October 2019, 55 patients were randomized, of whom 48 were evaluable (24 in each group). The median progression-free survival time using RECIST criteria was 18.6 months in patients treated with chemoembolization + preconditioning cyclophosphamide + DC infusions compared with 10.4 months in those treated with chemoembolization + preconditioning cyclophosphamide alone (HR = 0.43; upper value of one-sided 80% confidence interval, 0.57; P = 0.016). The addition of DC infusions did not significantly increase the incidence or severity of adverse events. An enhanced antigen (α-fetoprotein)-specific immune response was observed in patients treated with DC vaccination.

CONCLUSIONS

The addition of DC infusions to TACE and preconditioning cyclophosphamide has shown promising preliminary activity and merits further investigation in a larger randomized trial.