Immunotherapy Prolongs Hepatocellular Carcinoma Survival

Neil Osterweil

April 18, 2018

PARIS — For patients with hepatocellular carcinoma, adjuvant immunotherapy with autologous cytokine-induced killer cells significantly extends 5-year recurrence-free and overall survival, data from a follow-up extension study show.

"Surprisingly, the gain in survival was even after withdrawal of finite-duration immunotherapy," said Jeong-Hoon Lee, MD, PhD, from Seoul National University College of Medicine in South Korea.

The immunotherapy uses T-lymphocytes derived from a patient's peripheral blood. They are expanded ex vivo with cytokines and cytotoxic T-cells, and then reinfused into the patient at fixed intervals.

Lee reported follow-up results from a study of immunotherapy in patients with hepatocellular carcinoma treated with surgical resection, radiofrequency ablation, or percutaneous ethanol injection at university-affiliated hospitals in Korea here at the International Liver Congress 2018.

The original study showed that the primary end point of median recurrence-free survival was better with immunotherapy than with no adjuvant therapy (44 vs 30 months; hazard ratio [HR], 0.63; P = .010), as were the secondary end points of all-cause mortality (HR, 0.21; 95% confidence interval [CI], 0.06 - 0.75; P = .008) and hepatocellular carcinoma-related death (HR, 0.19; 95% CI, 0.04 - 0.87; P = .02) (Gastroenterology. 2015;148:1383-1391.e6).

Adverse events were significantly more common in the immunotherapy group than in the control group (62% vs 41%; P = .002), but the difference in serious adverse events between groups was not significant (7.8% vs 3.5%; P = .15).

In the immunotherapy group, cytokine-induced killer cells 200 mL were administered intravenously over a period of 60 minutes. The 16 treatments were delivered once weekly for the first 4 weeks, followed by four treatments every 2 weeks, four treatments every 4 weeks, and then four treatments every 8 weeks.

In the extension study, participants in the original study — 89 from the immunotherapy group and 73 from the control group — were followed out to a median of 68.5 months.

At 5 years, median recurrence-free survival continued to be better in the immunotherapy group than in the control group (44.8% vs 33.1%; HR, 0.67, P = .009), as did overall survival (HR 0.33; P = .006) and cancer-specific survival (HR, 0.33; = .02).

Most of the benefit was in patients with tumors at least 2 cm in size (HR, 0.66; = .035). Although there appeared to be some recurrence prevention in patients with lesions smaller than 2 cm, the difference was not statistically significant, possibly because of the relatively small sample size.

It is possible that the prolonged antitumor activity of cytokine-induced cells promotes long-lasting memory T-cells and memory natural killer cells, Lee explained. In fact, the cells themselves are a form of terminally differentiated memory T-cells, he added.

Cost is a barrier to the widespread adoption of this approach, he acknowledged, noting that in Korea, the procedure is not currently reimbursable.

Despite the cost, any effective and safe adjuvant therapy would be welcome in the management of patients with hepatocellular carcinoma, said Ronald Sokol, MD, from the University of Colorado School of Medicine in Aurora. To date, nothing has been proven to reduce the risk for recurrence.

"Once again, the results are quite impressive," Sokol told Medscape Medical News.

"In cancer trials, if you prolong your survival without recurrence by 14, 16, 18 months, that's frequently considered a very significant interval, particularly when drug combinations are eventually used and extend cancer-free survival," he said.

This study was supported by Green Cross Cell. Lee and Sokol have disclosed no relevant financial relationships.

International Liver Congress (ILC) 2018: Abstract GS-008. Presented April 13, 2018.

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