Randomized, multicenter, open-label trial of autologous cytokine-induced killer cell immunotherapy plus chemotherapy for squamous non-small-cell lung cancer
Overall Survival
Summary
This study investigates the clinical efficacy CIK cell immunotherapy plus chemotherapy in patients with advanced squamous non-small-cell lung cancer (NSCLC). This phase II study provides evidence for the efficacy and safety of CIK cell immunotherapy plus chemotherapy in patients with previously untreated, advanced squamous NSCLC.
Patients characteristics
90 patients with histologically confirmed staged IIIB and IV squamous non-small-cell lung cancer with ECOG performance status of <2. All patients has an adequate bone marrow, liver and renal function.
Methodology
All patients were assigned randomly to either the CIK cell immunotherapy plus chemotherapy group (CIK-CT group, n = 45) or the chemotherapy group (CT group, n = 45).
CIK cell preparation
PBMC were collected from lung cancer patients after surgery using a Cobe Spectra Apheresis System and cultured in X-VIVO 20 serum-free medium containing 50 ng/mL anti-CD3 antibody (Ab) to stimulate CIK cell growth, 100 U/mL recombinant human interleukin (IL)-1a and 1,000 U/mL recombinant human interferon (IFN)-c, at 37 °C with 5 % CO2 for 24 hours. Then, 300 U/mL recombinant human IL-2 was added to the media. IL-2- and IFN-c-containing medium was added to the culture system every 5 days. On day 14, CIK cells were harvested and analyzed for phenotype and cytotoxicity. Safety testing was performed during the course of cell culture.
Treatment
In patients of CIK-CT group, the median count of untreated PBMCs was 18.0 × 108 (range, 11.0 × 108 to 31.5 × 108) per cycle. The median count of autologous CIK cells after 15 days of amplification was 198.0 × 108 (range, 105.0 × 108 to 365.0 × 108) per cycle.
Results
The median PFS was 8.7 months (95% CI, 7.1 to 10.3) in the CIK-CT group and 4.0 months (95% CI, 3.1 to 5.0) in the CT group. Subgroup analyses showed that the PFS in CIK-CT group was better than that in CT group in most of the sub-groups analyzed. The median OS was 21.0 months (95% CI, 17.8 to 24.2) in the CIK-CT group and 10.3 months (95% CI, 7.9 to 12.1) in the CT group. Subgroup analyses showed that the OS in CIK- CT group was better than that in chemotherapy group in most of the sub- groups analyzed.
The ORR (CR + PR) was 62.2% (95% CI, 47.9 to 76.5%) in the CIK-CT group and 31.1% (95% CI, 17.4 to 44.8%) in the CT group. The median duration of response was 9.6 months (range, 1.5+ to 53.0+) in the CIK-CT group and 5.0 months (range, 1.5 to 10.0) in the CT group.
Adverse events
Adverse events (AEs) of any grade were no difference between in the CT group (100%) and in the CIK- CT group (93.3%) (P = 0.356). AEs of grade 3 or 4 occurred in 42.2% of the patients in the CT group and in 33.3% of the patients in the CIK-CT group (P = 0.296); led to the discontinuation of all treatment components in 15.6 and 4.4%, respectively; and led to dose reduction of chemotherapy in 11.1 and 15.6%.
Conclusion
This phase II study provides evidence for the efficacy and safety of CIK cell immunotherapy plus chemotherapy in patients with previously untreated, advanced squamous NSCLC.