Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma: an extended 5-year follow-up

Jeong Hoon Lee, Joon Hyeok Lee, Young Suk Lim, Jong Eun Yeon, Taejin Song, Su Jong Yu, Geum Youn Gwak, Kang Mo Kim, Yoon Jun Kim, Jae Won Lee, Jung Hwan Yoon

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Our earlier multicenter randomized controlled trial showed that adjuvant immunotherapy with cytokine-induced killer (CIK) cells resulted in longer recurrence-free survival (RFS) and overall survival (OS) as well in patients who received curative treatment for hepatocellular carcinoma (HCC). In the present study, we determined if the efficacy of CIK cell therapy continued after end of repeated CIK cell injections. We performed a follow-up study of our preceding trial. We included 226 patients: 114 patients in the immunotherapy group (injection of 6.4 × 109 CIK cells, 16 times during 60 weeks) and 112 patients in the control group (no treatment) after potentially curative treatment for HCC. In total, 162 patients (89 of the immunotherapy group and 73 of controls) underwent an extended follow-up for 60 months after randomization of the last patient. The primary endpoint was RFS, and secondary endpoints included OS. During follow-up time of median 68.5 months (interquartile range 45.0–82.2 months), the immunotherapy group continued to show a significantly lower risk of recurrence or death [hazard ratio (HR) 0.67; 95% confidence interval (CI) 0.48–0.94; P = 0.009 by one-sided log-rank test]. At 5 years, RFS rate was 44.8% in the immunotherapy group and 33.1% in the control group. The risk of all-cause death was also lower in the immunotherapy group compared to the control group (HR 0.33; 95% CI 0.15–0.76; P = 0.006). In patients who received curative treatment for HCC, the significant improvement in RFS and OS as a result of adjuvant CIK cell immunotherapy lasted over 5 years without boosting.

Original languageEnglish
JournalCancer Immunology, Immunotherapy
Publication statusAccepted/In press - 2018 Jan 1



  • Adjuvant immunotherapy
  • Cytokine-induced killer cell
  • Hepatocellular carcinoma
  • Overall survival
  • Recurrence-free survival

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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