Efficacy and Safety of Lenvatinib in Patients with Recurrent Hepatocellular Carcinoma after Liver Transplantation

410 Background: Lenvatinib is approved for use in patients with metastatic or recurrent hepatocellular carcinoma (HCC); however, its clinical outcomes in patients experiencing HCC recurrence after liver transplantation (LT), remain unclear. Further, despite of immunotherapeutic advances (atezolizumab plus bevacizumab, pembrolizumab, and nivolumab) in the management of advanced HCC, patients with prior LT are not benefited because of the risk of allograft rejection, and they are also excluded in the most prospective clinical trials for novel agents. Thus, we investigated the efficacy and safety of lenvatinib treatment in patients with recurrent HCC after LT. Methods: This single center, retrospective study included 22 patients with recurrent HCC after LT who received lenvatinib at the Asan Medical Center, South Korea, between November 2019 and March 2021. Lenvatinib was given 12mg/day for bodyweight ≥ 60 kg or 8 mg/day for bodyweight < 60 kg. Response and adverse events (AEs) were graded according to RECIST v1.1 and NCI CTCAE v5.0. Results: The median age was 58 years (range, 20-69) and 95.5% (n = 21) were male. Most common etiology of HCC was hepatitis B (n = 18, 81.8%). The median time to recurrence after LT was 6.6 months (95% CI, 4.2-9.1 months). Prior to systemic therapy, transarterial embolization (TACE) (n = 12, 54.5%) was the most commonly used therapy for recurred HCC after LT. At the time of lenvatinib initiation, 95.5% (n = 21) of the patients were Child-Pugh A with 15 (68.2%) and 7 (31.8%) patients classified as ALBI grades 1 and 2, respectively. All patients were at BCLC stage C and lenvatinib was administered as first-line (n = 19) and second-line (n = 3) therapy. The objective response rate (ORR) was 13.6%. With a median follow-up duration of 5.2 months (range, 1.7-14.5 months), the median progression-free survival (PFS) was 6.6 months (95% CI: 3.6-9.5 months) and overall survival (OS) was 14.5 months (95% CI: not assessable). The 6-month PFS and OS rates were 59.8% and 88.8%, respectively. Patients with ALBI grade 2 showed significantly poorer OS [11.1 months (95% CI: not assessable)] compared to patients with ALBI grade 1 [14.5 months (95% CI: not assessable)] ( p= 0.011). AEs were hypertension (n = 8, 36.4%), thrombocytopenia (n = 7, 31.8%), and fatigue (n = 6, 27.3%). Conclusions: Lenvatinib was effective and showed manageable toxicities in patients with recurrent HCC after LT. These outcomes are comparable to those from the pivotal REFLECT trial where patients with LT were excluded. Better baseline liver function (ALBI grade 1) at lenvatinib initiation correlated with better survival outcomes.