A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

Abstract

Background & Aims: There is no generally accepted adjuvant therapy for hepatocellular carcinoma (HCC) after curative resection. Autologous cytokine-induced killer (CIK) cells therapy has been reported to improve outcomes of patients with HCC, but its role as an adjuvant therapy remains unclear. This study aimed to evaluate the efficacy and safety of CIK as an adjuvant therapy for HCC after curative resection.Methods: This is a single center, phase 3, open label, randomized controlled trial (RCT). Two hundred patients who were initially diagnosed with HCC of Barcelona Clinic Liver Cancer (BCLC) stage A or B, and underwent curative hepatectomy were randomly assigned to receive four cycles of CIK treatment (the CIK group, n D 100) or no treatment (the control group, n D 100). The primary outcome was time to recurrence. The secondary outcomes included disease-free survival (DFS), overall survival (OS) and adverse events.Results: All patients in the CIK group finished the treatment by protocol. The median time to recurrence (TTR) was 13.6 (IQR 6.5-25.2) mo in the CIK group and 7.8 (IQR 2.7-17.0) mo in the control group (p D 0.01). There were no significant differences between the groups in DFS and OS. All adverse events were grade 1 or 2. There were no significant differences in incidence between the two groups.Conclusions: Four cycles of CIK therapy were safe and effective to prolong the median TTR in patients with HCC after curative resection, but the treatment did not improve the DFS and OS.

Timely meta-analysis on the efficacy of adoptive immunotherapy for hepatocellular carcinoma patients after curative therapy

“…The discrepancy between our findings and those of previous systematic reviews likely reflects the more than two decades spanned by the literature, with the first randomized trial on adjuvant AIT for HCC after surgery published in 1995 [41,44] and the most recent in 2016 [23], combined with rapid scientific and technological advances in AIT [53,54]. In addition, no international guidelines or standards exist regarding route of AIT administration, dosing, or cycles.…”

“…Two studies including patients who underwent transarterial chemoembolization were also excluded [24,45]. In the end, 7 RCTs [22,23,40–44] and one cohort studies [25] involving 949 AIT-treated and 912 untreated patients were included in the meta-analysis (Fig 1, Table 1). …”

“…Meta-analysis of all 8 studies [22,23,25,40–44] suggested that adjuvant AIT was associated with significantly lower recurrence rate than curative therapies alone at 1 year (Fig 3), 2 years, 3 years, and 5 years (Table 2). Similar results were obtained using a random- or fixed-effects meta-analysis model.…”

“…Four RCTs [22,23,40,42] had a high methodological quality score (≥3) and three RCTs [41,43,44] had a low methodological quality score (≤2). Owing to the difficulties in blinding the intervention, none of the RCTs were able to score the maximum of five points; therefore a score of three, which is classified as high methodological quality, was the maximum score possible.…”

Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2017 Edition)

“…[66], checkpoint inhibitors (CTLA-4 antibody, PD-1/PD-L1 antibody) [118], tumor vaccines (dendritic cell vaccines, etc. ), adoptive immunotherapy (cytokine-induced kill cells) [117, 119]. These treatment approaches have been used for HCC patients.…”