Starting in 2008, Jeong-Hoon Lee of Seoul National University College of
Medicine in South Korea and colleagues conducted a Phase
3 trial of the safety and efficacy of adjuvant immunotherapy in people with HCC
who had undergone surgical resection, radiofrequency ablation or percutaneous
The study included 230 participants
enrolled at university hospitals in Korea. More than 80% were men and the mean
age was approximately 56 years. Over 80% had hepatitis B and about 10% had
hepatitis C; two thirds had liver cirrhosis. About 85% had stage 1 HCC and the
rest had stage 2. Most had fewer than three tumours, with a median size of
about 2 cm.
Participants in this open-label study were
randomly assigned to receive immunotherapy or no adjuvant treatment. The
immunotherapy consisted of activated cytokine-induced killer cells created by
incubating collected T cells with interleukin 2 and an antibody against CD3. Previous
studies showed that cytokine-induced killer cells, which have the
functional capacity of both T cells and natural killer cells, are active
against various tumour types with little effect on normal cells. The
activated cells were given intravenously 16 times over 60 weeks.
As reported in 2015, people who received adjuvant
immunotherapy had significantly longer recurrence-free survival than those in
the control group (44 vs 30 months, respectively), as well as a lower risk of
all-cause and cancer-related mortality. People in the immunotherapy group
were more likely to experience adverse events (62% vs 41%, respectively), but
serious adverse events were uncommon in both study arms.
At this year's meeting, Lee reported
findings from an extended follow-up study to assess whether the efficacy of cytokine-induced
killer cell immunotherapy would be sustained after
completion of treatment.
A total of 162 participants (89 in the immunotherapy group and 73 in the control group) underwent
extended follow-up, which ended 60 months after the last participant was
randomised, for a median follow-up duration of about 69 months.
During follow-up, people who received
the immunotherapy had a significant 33% lower risk of HCC recurrence or death.
The 5-year recurrence-free survival rate was 45% in the immunotherapy group
versus 33% in the control group. Overall mortality was reduced by 67%. The
benefit was most apparent for people with tumours measuring 2cm or more.
"In patients who underwent curative
treatment for HCC, significant gain in recurrence-free and overall survival by
adjuvant cytokine-induced killer cell immunotherapy was maintained for over 5 years," the researchers
Lee suggested that the treatment might
promote the development of long-lasting memory T cells and natural killer cells
that can carry on anti-tumour activity for years after the last immune cell