Editor's Note: Immune checkpoint inhibitors (ICI) are gradually becoming a key therapeutic strategy in the neoadjuvant treatment of advanced hepatocellular carcinoma (HCC). Their widespread application reflects the deep understanding and continuous innovation in HCC treatment within the medical community, offering new hope and possibilities for countless patients. Recently, the Journal of Hepatology (JOH) published the important findings of the VITALITY study, a multi-center clinical study conducted by several leading medical centers in the United States. This study assessed the efficacy and safety of ICI treatment in HCC patients before liver transplantation. Led by r Parissa Tabrizian and her team from the Recanati/Miller Transplantation Institute at the Icahn School of Medicine at Mount Sinai, New York, the results demonstrated encouraging survival rates and safety outcomes for ICI treatment before liver transplantation.ICI works by disrupting inhibitory immune pathways in the tumor microenvironment, reactivating the body’s own antitumor immune responses, and thereby effectively killing tumor cells. This mechanism has allowed ICIs to exhibit remarkable efficacy in patients with advanced HCC. Large clinical trials such as CheckMate-040, Keynote-224, and IMbrave150 have all confirmed the significant advantages of ICIs in prolonging patient survival, improving disease control rates, and enhancing quality of life.
In addition, compared to traditional chemotherapy drugs, ICIs generally have better tolerance and a lower incidence of severe toxic reactions. Although some patients may experience immune-mediated adverse reactions such as pneumonia, hepatitis, or dermatitis, these reactions are mostly reversible and can be effectively managed through timely diagnosis and intervention. With an increasing understanding of the mechanisms and side effects of ICIs, clinicians are now better equipped to predict and manage these adverse events, thus improving the safety and compliance of treatments.
As clinical research progresses, personalized treatment is becoming a key trend in the neoadjuvant use of ICIs in HCC. Given the variability in tumor characteristics, immune status, and comorbidities in each patient, individualized treatment plans are essential. This includes selecting the most suitable ICI drug, determining the optimal dosage and frequency, and evaluating the efficacy of combining ICIs with other therapies. Personalized treatment maximizes the efficacy of ICIs while minimizing adverse effects, thus improving both survival rates and patient outcomes.
The widespread use of ICIs in advanced HCC has brought attention to their potential as a bridging and downstaging strategy before liver transplantation. However, most current studies in this field are small and single-center, with varying results. The VITALITY study is the world’s first multi-center, large-scale clinical trial evaluating the safety and intention-to-treat (ITT) outcomes of ICI treatment before liver transplantation.
The study included 117 consecutive HCC patients evaluated for liver transplantation between 2016 and 2023, all of whom received ICI treatment before surgery. The researchers conducted both ITT and survival analyses, while also assessing rejection rates post-transplantation.
Key Findings:
- Significant Downstaging Effect: Of the 117 patients, 86 (73.5%) initially exceeded the Milan criteria, but 65 (75.6%) successfully downstaged after ICI treatment, with a median downstaging time of 5.6 months.
- Transplant Success Rate: Ultimately, 43 patients (36.7%) underwent liver transplantation, including 18 patients (15.4%) who initially met the Milan criteria and 23 patients (19.7%) who met the criteria after successful downstaging.
- High Safety: No grade 4 or 5 serious adverse events occurred while waiting for liver transplantation. The study also identified high tumor burden, doubling of alpha-fetoprotein (AFP) levels, and radiographic response as independent predictors for removal from the transplant waitlist.
- Excellent Survival Rates: The study showed an ITT 3-year survival rate of 71.1%, with 73.5% for those within the Milan criteria and 69.7% for those who initially exceeded the criteria (P=0.329). The post-transplantation 3-year survival rate was 85%.
- Rejection Rates: Post-transplantation, seven patients experienced rejection, six of whom had received their last dose of ICI within three months before transplantation, resulting in one graft loss.
Commentary by Dr. Parissa Tabrizian:
“The widespread use of ICIs is gradually transforming the treatment paradigm for HCC. Traditional HCC treatments, including surgery, radiotherapy, and chemotherapy, have limited efficacy in treating advanced HCC and are often accompanied by high toxicity and side effects. The advent of ICIs offers a new treatment avenue for patients with advanced HCC, enabling the possibility of combination therapies. By integrating ICIs with locoregional therapies, targeted therapies, liver resection, or liver transplantation, a multi-tiered antitumor strategy can be established to further improve treatment outcomes and patient survival rates.”
“This is the first multi-center study evaluating the effects of ICI treatment before liver transplantation in HCC patients, and the results demonstrate good survival and safety profiles. These findings support the continued use and further investigation of this strategy in clinical practice. The study suggests that ICIs, either as monotherapy or combined with locoregional therapies, may be particularly beneficial for high-risk patients, especially those requiring downstaging or whose AFP levels remain elevated after locoregional treatment. These results could potentially revolutionize future management strategies for HCC, and we look forward to ongoing clinical trials that may further validate these outcomes.”
Future Outlook:
With a deeper understanding of the mechanisms of ICIs and tumor immune evasion, and the development of more innovative ICI drugs and therapeutic strategies, the prospects for ICIs in the neoadjuvant treatment of advanced HCC appear increasingly promising. More clinical studies are needed to confirm the efficacy and safety of ICIs in different patient populations, leading to the development of more scientifically sound and rational treatment protocols that will benefit a broader group of HCC patients.
