Feasibility and effectiveness of liver transplantation following immunotherapy in patients with hepatocellular carcinoma

Abstract

Introduction

Immunotherapy is an attractive strategy for downstaging/bridging hepatocellular carcinoma (HCC) to liver transplantation (LT).

Aims

This multicenter study reports the results of HCC-transplanted patients in ten French liver transplant centers in this context.

Patients and Methods

Clinical, biological, and radiological data were collected for each patient at the beginning and end of immunotherapy and before LT. The primary endpoint was the tolerance and effectiveness of LT.

Results

Twenty-one patients [majority of men (17/21); median age 62 years (57-64), BCLC B stage in 14/21 patients (66.7%)] who underwent LT for HCC after immunotherapy were included. HCC was multi-nodular in 17/21 (81%) cases, with a median size of the largest nodule of 36 mm (21-60). Thirteen patients had an AFP score >2 (downstaging group) and 8 of ≤2 (bridging group). Patients in the downstaging group were beyond Milan criteria, and 3 in the bridging group (p=0.006). Sixteen patients (76.2%) received Atezolizumab/Bevacizumab during 8.5 cycles (4.7-14). At the end of immunotherapy, most patients shifted to an early/intermediate BCLC stage (p=0.001) and reached Milan criteria (57.1%, p=0.023). The AFP score remained >2 in 2 cases (9.5%) (p=0.003). The median interval between the last immunotherapy cycle and LT was 5.1 (2.7-9.3) months. All patients except 3 received standard immunosuppressive treatment. Two cases (10%) of rejection occurred, resolved after increasing immunosuppression. Early serious adverse events occurred in 6 patients (28.5%), 5 being fatal (27%). Two patients (10.5%) had an HCC recurrence post-LT. On explant pathology, no residual tumor was detected in 6 cases (28.6%) and partial necrosis in 7 (41.2%). The R3-AFP score stratified patients into 3 at very low (14.3%), 8 at low (38.1%), and 10 at high (47.6%) recurrence risk.

Conclusion

LT following immunotherapy is feasible in selected patients with HCC and has an acceptable risk of rejection. However, the high immediate mortality observed requires further exploration in prospective studies.