麻豆果冻传媒影音

Patients with hepatocellular carcinoma (HCC) achieved promising outcomes when treated with immunotherapy prior to liver transplant, a prospective study showed.

Among 64 patients who received immune checkpoint inhibitors, 78% had downstaging of their liver tumor to within , and 37% went on to liver transplant, reported Parissa Tabrizian, MD, MSc, of the Icahn School of Medicine at Mount Sinai in New York City.

Despite the small number of patients who eventually went to transplant, survival outcomes with pre-transplant immunotherapy were "encouraging," Tabrizian said during a session at the American Association for the Study of Liver Diseases annual meeting in San Diego.

In explaining the rationale for this study, Tabrizian noted that the demonstrated that patients with HCC who had their tumors downstaged prior to transplant had superior survival outcomes.

Previous results from the (MERITS-LT) Consortium, which evaluated patients with tumor burden within United Network for Organ Sharing downstaging (UNOS-DS) criteria (tumors ≤8 cm, with no vascular invasion or extrahepatic spread), showed a downstaging rate of over 80%.

An evaluation of an -- patients with tumors of any number, size, and diameter, with a wait time of 6 months prior to transplant -- from the same consortium also showed "acceptable" survival outcomes, Tabrizian said.

At the same time, immune checkpoint inhibitors in patients with advanced HCC have shown promising results. In the EMERALD-1 trial, the use of transarterial chemoembolization (TACE) combined with durvalumab (Imfinzi) with or without bevacizumab (Avastin) in participants with unresectable HCC eligible for embolization demonstrated statistically significant and clinically meaningful improvements in progression-free survival compared with TACE alone.

Tabrizian said that this leads to the question of whether immunotherapy can be used as a bridge to transplantation. "Are we going to improve outcomes compared to standard locoregional therapies?" she asked.

The current study included three groups -- 201 patients with tumor burden within UNOS-DS criteria, 122 in an all-comers cohort, and the 64 patients who underwent immunotherapy. All were treated at eight transplant centers and enrolled prospectively from 2015-2024.

Patients with complete response to first locoregional therapy (LRT) were excluded from the study, as were patients who received immunotherapy alone, and those with macrovascular invasion and extrahepatic disease. Immune checkpoint inhibitors were used in patients who exhausted LRT options or had more aggressive tumor biology.

Median age at first treatment (63-64), sex (80-86% men), underlying liver disease (49-52% hepatitis C virus), Child-Pugh scores (73-78% with a score of A), and median alpha-fetoprotein levels (12-16.5 ng/mL) were similar across the groups. The median total tumor diameter was 8.8 cm in the immunotherapy group, 6.4 cm in the UNOS-DS group, and 9.4 cm in the all-comers group. About one-third of patients had undergone four or more pre-transplant LRTs.

Among the immunotherapy patients, half received nivolumab (Opdivo), 23.4% received atezolizumab (Tecentriq) plus bevacizumab, 20.3% received pembrolizumab (Keytruda), and 6.3% received tremelimumab (Imjudo) plus durvalumab. The duration of immunotherapy was 7.3 months.

The median time to downstaging with immunotherapy was 7.2 months compared with 3 months in the UNOS-DS group and 4.7 months in an all-comers group (P<0.001).

The cumulative probability of waitlist dropout at 3 years was similar among the groups: 48.3% in the immunotherapy group, 42.9% in the UNOS-DS group, and 46.9% in the all-comers group.

The probability of liver transplantation was 29.5%, 46.8%, and 50.9%, respectively (P=0.0276), and the probability of downstaging at 3 years was 78.3%, 92.4%, and 88.1%, respectively (P=0.0004).

The post-liver transplant survival rate at 3 years was not significantly different, at 93.8% in the immunotherapy group, 83.6% in the UNOS-DS group, and 81.9% in the all-comers group.

The intention-to-treat survival rate at 3 years was also not significantly different, at 71.7% in the immunotherapy group, 68.8% in the UNOS-DS group, and 61.7% in the all-comers group. "So, some signal that it [preoperative immunotherapy] may be better, but not statistically significant," Tabrizian noted.

No grade 4/5 immune checkpoint inhibitor-related adverse events occurred on the waitlist, with 50% of patients receiving their last dose less than 1 month before liver transplant. Three immunotherapy patients experienced post-liver transplant rejection.

Tabrizian acknowledged the study had several limitations. "It is a small cohort," she said. "There are biases in terms of selection, as well as the heterogeneity of the immunotherapy used -- some were not standard of care."

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