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Clinical Trial
. 2015 Jan;64(1):51-9.
doi: 10.1007/s00262-014-1613-0. Epub 2014 Sep 28.

Randomized controlled phase III trial of adjuvant chemo-immunotherapy with activated killer T cells and dendritic cells in patients with resected primary lung cancer

Hideki Kimura  1 , Yukiko Matsui, Aki Ishikawa, Takahiro Nakajima, Mitsuru Yoshino, Yuichi Sakairi
Affiliations
Clinical Trial

Randomized controlled phase III trial of adjuvant chemo-immunotherapy with activated killer T cells and dendritic cells in patients with resected primary lung cancer

Hideki Kimura et al. Cancer Immunol Immunother. 2015 Jan.

Abstract

Purpose: We conducted a phase III randomized controlled trial (RCT) to investigate the efficacy of postsurgical adjuvant immunotherapy combined with chemotherapy. The immunotherapy targets were residual micrometastases and clones resistant to chemotherapy.

Patients and methods: Between April 2007 and July 2012, 103 postsurgical non-small cell lung cancer patients were randomly assigned to receive either chemo-immunotherapy (group A) or chemotherapy (group B). The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients' own regional lymph nodes.

Results: The 2-year overall survival rates in groups A and B were 93.4 and 66.0 %, and the 5-year rates were 81.4 and 48.3 %, respectively. The differences were statistically significantly better in group A. The hazard ratio (HR) was 0.229 (p = 0.0013). The 2- and 5-year recurrence-free survival rates were 68.5, 41.4 and 56.8, 26.2 % in groups A and B, respectively. Those differences were also statistically significant (log-rank test p = 0.0020). The HR was 0.423 (p = 0.0027) in favor of group A. As for adverse reactions to immunotherapy, of a total of 762 courses, 52 (6.8 %) were accompanied with chills and shivering, and 47 (6.2 %), with fever (>38 °C).

Conclusions: Immunotherapy has the potential to improve the postsurgical prognosis of lung cancer patients, but a large-scale multi-institutional RCT is awaited for further confirmation of this study.

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Figures

Fig. 1
Fig. 1
CONSORT diagram. Out of 556 cases treated surgically from April 2007 to July 2012, 103 eligible cases were randomized to receive chemo-immunotherapy (group A) or chemotherapy (group B). Ineligible cases (1 case each in groups A and B) were excluded, and 50 and 51 group A and B cases, respectively, were treated
Fig. 2
Fig. 2
Procedure for chemo-immunotherapy. Tumor-draining regional lymph nodes (TDLN) with no metastasis were obtained at surgery, minced aseptically, and cultured in lymphocyte medium containing IL-2. Activated killer T cells and dendritic cells (AKT-DC) released from TDLN were harvested, washed, and transferred to the patients every month, beginning 1 week after adjuvant chemotherapy for 4 courses. Immunotherapy was continued every month for 6 months and then every 2 months until 2 years after surgery. When TDLN stopped releasing AKT-DC, peripheral blood lymphocytes obtained by lymphocyte apheresis were added and co-cultured with TDLN
Fig. 3
Fig. 3
Kaplan–Meier estimates of overall survival for groups A and B
Fig. 4
Fig. 4
Kaplan–Meier estimates of recurrence-free survival for groups A and B
See this image and copyright information in PMC

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