Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data

Abstract

BackgroundStudies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain.MethodsWe constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses.ResultsBased on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER.ConclusionWe showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.

2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma

“…913 In a cost-effectiveness analysis study based on the results of the randomized controlled study and the realworld study, the incremental cost-effectiveness ratio were $33,077/QALY (quality-adjusted life-year) and $25,107/QALY, respectively. 814 In a Chinese randomized controlled phase 3 trial, CIK cell treatment significantly prolonged the time-torecurrence (13.6 months in the CIK group and 7.8 months in the control group, P=0.01); however, in this study, no statistically significant differences were observed in either RFS or OS. 907 A meta-analysis of the RCTs reported that adjuvant CIK cell therapy significantly improved RFS and OS up to 3 years in patients after curative treatment.…”

“…It is recommended to interrupt lenvatinib if 24hour urinary protein is ≥2 g. If a dipstick proteinuria result of 2+ or more is detected, a random urinary protein to creatinine ratio can be used to monitor proteinuria before further testing with the 24-hour urinary protein. 813,814 Thyroid stimulating hormone (TSH) levels should be monitored. If the TSH level is higher than 10 mIU/L or higher than 5 mIU/L on two separate occasions, consultation with an endocrinologist should be considered.…”

“…If the TSH level is higher than 10 mIU/L or higher than 5 mIU/L on two separate occasions, consultation with an endocrinologist should be considered. 814,815 Hypertension or HFSR has been reported as a predictor of better prognosis, and the OS in patients who discontinued lenvatinib due to SAEs was significantly shorter than those who continuously received treatment. 816 When patients were divided into those with objective response and those without, relative dose intensity was significantly higher in patients showing objective response to lenvatinib.…”

“…In a Korean real-world study using propensity score analysis, CIK adjuvant therapy significantly improved RFS (HR, 0.42; 95% CI, 0.22–0.80, P =0.006) [ 913 ]. In a cost-effectiveness analysis study based on the results of the randomized controlled study and the realworld study, the incremental cost-effectiveness ratio were $33,077/QALY (quality-adjusted life-year) and $25,107/QALY, respectively [ 814 ]. In a Chinese randomized controlled phase 3 trial, CIK cell treatment significantly prolonged the time-to-recurrence (13.6 months in the CIK group and 7.8 months in the control group, P =0.01); however, in this study, no statistically significant differences were observed in either RFS or OS [ 907 ].…”

2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma

“…Other adverse events frequently observed in the lenvatinib group were diarrhea (39%), anorexia (34%), weight loss (31%), fatigue (30%), proteinuria (25%), and hypothyroidism (16%). It is recommended to interrupt lenvatinib if 24-hour urinary protein is ≥ 2 g. If a dipstick proteinuria result of 2+ or more is detected, a random urinary protein to creatinine ratio can be used to monitor proteinuria before further testing with the 24-hour urinary protein [ 813 814 ]. Thyroid stimulating hormone (TSH) levels should be monitored.…”