Immunotherapy may make transplant possible in late-stage liver cancer
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Key takeaways:
- Acceptable liver transplant outcomes after immune checkpoint inhibitor therapy can be achieved.
- Age and length of washout period may affect allograft rejection risk.
Immunotherapy treatment may make liver transplant viable for patients with later-stage hepatocellular carcinoma provided they adhere to a 3-month waiting period, according to study results.
Liver transplant is the optimal treatment for liver cancer; however, it historically has only been available to patients with early-stage disease.
“Since 2020, several reports from around the world have looked at using immune checkpoint inhibitors before liver transplantation,” Ju Dong Yang, MD, medical director of the liver cancer program at Cedars-Sinai, told Healio.
However, there has been concern that use of immune checkpoint inhibitors may increase risk for allograft rejection or have a detrimental effect on other outcomes.
Yang and colleagues used databases to identify patients with HCC who received immune checkpoint inhibitors prior to liver transplant.
They performed a meta-analysis of individual patient data to assess allograft rejection, hepatocellular recurrence rates and OS. They also sought to identify factors that may increase risk for allograft rejection.
The analysis included 91 eligible patients with median follow-up of 690 days.
Twenty-four patients (26.4%) experienced allograft rejections, nine (9.9%) experienced hepatocellular carcinoma recurrence and nine (9.9%) died.
Researchers identified two factors associated with allograft rejection — age (adjusted HR per 10 years = 0.72; 95% CI, 0.53-0.99) and immune checkpoint inhibition washout time (adjusted HR per 1 week = 0.92; 95% CI, 0.86-0.99).
Analyses of patients with 20% or lower probability of allograft rejection showed a median washout period in this group of 94 days.
OS did not differ between patients with or without allograft rejection.
“Using immune checkpoint inhibitors before a liver transplant generally carries an acceptable risk [for] rejection, cancer recurrence and death for [people with liver cancer],” Yang said.
“The risk of the body rejecting the new liver seemed lower when there was a longer wait between the last immune checkpoint inhibitor dose and the transplant,” Yang added. “However, even with a long wait, some rejections still occurred, suggesting there may be other factors at play.”
Patients who developed liver cancer recurrence had fewer median cycles of immune checkpoint inhibitor therapy than those who did not develop recurrence (4 vs. 8).
The proportion of patients with tumor burden within Milan criteria after completion of immune checkpoint inhibitor therapy was lower in the recurrence group than the non-recurrence group (16.7% vs. 65.3%; P = .032).
Researchers acknowledged study limitations.
“Most of the data came from small case reports or small studies without control groups, which makes it hard to draw strong conclusions,” Yang told Healio. “We also might have missed some negative outcomes because positive results are often more likely to be reported. Furthermore, many cases did not have confirmed rejection through biopsy, so it’s unclear if rejection is directly due to immune checkpoint inhibitors.”
Additional studies are needed to confirm the findings, Yang said.
“In future research, we need to figure out which patients are most likely to benefit from immune checkpoint inhibitors before a liver transplant, based on factors like their cancer type and stage,” Yang said. “It’s also important to determine the best time to start immune checkpoint inhibitors and how to combine them with other treatments. Many new studies and trials are already working on these questions.
“Additionally, future studies should explore how to best manage medications after the transplant, taking into account the specifics of immune checkpoint inhibitor treatment,” he added. “Overall, more research is needed to provide clearer answers and improve patient care.”
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Rezaee-Zavareh MS H, et al. J Hepatol. 2024;doi:10.1016/j.jhep.2024.06.042.
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