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Targeted immunotherapy and tumor immunogenicity in liver transplant recipients: A study on lenvatinib and PD-L1
Chao Ma1, Chaolu Li2, Haitao Zhang1
1Department of General Surgical Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China.
Background:
Long-term immunosuppression from transplants which reduces the body's ability to detect and fight the tumor, is the main reason hepatocellular carcinoma (HCC) often recurs.
Objectives:
This study evaluates the ability of lenvatinib (used to manage angiogenesis) and an anti-PD-L1 agent to help treat recurrent or new liver cancer in patients who have undergone LT.
Methods:
Participants of this retrospective cohort study included 15 people who had received a transplant and were treated with low-dose tacrolimus, 8-12 mg of lenvatinib and atezolizumab delivered through a vein every three weeks. Clinical data collected were overall survival (OS), progression-free survival (PFS), ORR, instances of tumor recurrence and events of adverse reactions related to treatment. Flow cytometry, Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to estimate the presence of CD8+ T cells, Tregs (Treg) and cytokine levels in tissues.
Results:
The data showed that the median OS was 36 months, almost twice as high as the data from sorafenib and the PFS time was 12 months, also substantially higher. At 12 months, 60% of patients improved by at least 50% in their scan (13.3% were free from disease while 46.7% improved) and the disease returned only in 20% of patients. Analysis found higher numbers of CD8+ T-cells in tumors (p=0.004), lower Treg cell numbers (p=0.008), increased IFN-γ and TNF-α and decreased IL-10. At the same time, there was a sharp decline in circulating tumor DNA (ctDNA) which followed decrease in imaging abnormalities. Severe acute rejection of the graft did not occur; adverse effects from therapy were addressed.
Conclusion:
This combination shows promising effects and good safety in patients with HCC who have received liver transplants. Such a method offers a fresh choice for treating those who are thought not to be suitable for immunotherapy, so it needs to be tested in more extensive controlled research.
Insights
This study shows that combining lenvatinib and atezolizumab may effectively treat recurrent liver cancer (HCC) after liver transplants, improving survival and showing good safety. This offers a new treatment option for patients not typically suited for immunotherapy.
Area of Science:
- Hepatocellular Carcinoma Research
- Immunotherapy
- Transplant Oncology
Background:
- Long-term immunosuppression post-liver transplant (LT) impairs anti-tumor immunity, leading to frequent hepatocellular carcinoma (HCC) recurrence.
- Identifying effective treatments for recurrent HCC in LT patients is crucial.
Purpose of the Study:
- To evaluate the efficacy and safety of lenvatinib plus atezolizumab in treating recurrent or new HCC after LT.
- To assess the impact of this combination therapy on patient survival and immune markers.
Main Methods:
- Retrospective cohort study of 15 LT patients treated with low-dose tacrolimus, lenvatinib, and atezolizumab.
- Clinical outcomes (OS, PFS, ORR) and adverse events were recorded.
- Tumor immune microenvironment was analyzed via flow cytometry, ELISA, and immunohistochemistry for CD8+ T cells, Tregs, and cytokines.
Main Results:
- Median Overall Survival (OS) was 36 months, and Progression-Free Survival (PFS) was 12 months, significantly higher than sorafenib benchmarks.
- Objective Response Rate (ORR) at 12 months was 60%, with disease recurrence in only 20% of patients.
- Treatment correlated with increased CD8+ T cells, decreased Tregs, elevated IFN-γ and TNF-α, decreased IL-10, and reduced circulating tumor DNA (ctDNA).
Conclusions:
- Lenvatinib and atezolizumab combination demonstrates promising efficacy and favorable safety for HCC post-LT.
- This approach provides a potential new therapeutic avenue for patients ineligible for standard immunotherapy.
- Further extensive, controlled research is warranted to validate these findings.
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