Takahashi Hidenori, Shimodaira Shigetaka, Ogasawara Masahiro, Ota Shuichi, Kobayashi Masanori, Abe Hirofumi, Morita Yuji, Nagai Kazuhiro, Tsujitani Shunichi, Okamoto Masato, Suzuki Yukio, Nakanishi Yoichi, Yonemitsu Yoshikazu
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Cancer Immunol Immunother. 2016 Sep;65(9):1099-111. doi: 10.1007/s00262-016-1872-z. Epub 2016 Jul 22.
The J-SICT DC Vaccine Study Group provides dendritic cell (DC) vaccines for compassionate use under unified cell production and patient treatment regimens. We previously reported beneficial effects of DC vaccines on the overall survival of 62 patients with advanced non-small cell lung cancer (NSCLC) in a single-center analysis. Here, we extended analysis to 260 patients with NSCLC who were treated at six centers.
Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks.
The mean survival time (MST) from diagnosis was 33.0 months (95 % confidence interval [CI]: 27.9-39.2), and that from time of first vaccination was 13.8 months (95 % CI 11.4-16.8). An erythema reaction at the injection site that was ≥30 mm in diameter was correlated most strongly with overall survival from the first vaccine (≥30 vs. < 30 mm: MST 20.4 vs. 8.8 months, P < 0.001). We reported a similar finding in our previous analysis of patients with advanced pancreatic cancer. Interestingly, although such findings were common between patients with adenocarcinoma and those with other subtypes, the former group experienced significantly prolonged overall survival and a higher response rate for erythema (56.3 vs. 37.3 %, respectively, P = 0.014).
This is the first multicenter study that suggests a possible clinical benefit of DC vaccines for patients with advanced NSCLC, especially those with adenocarcinoma. These findings suggest a specific potential responder population for DC vaccines and warrant further investigation in well-controlled prospective randomized trials.
J-SICT DC疫苗研究小组按照统一的细胞生产和患者治疗方案提供树突状细胞(DC)疫苗用于同情用药。我们之前在一项单中心分析中报告了DC疫苗对62例晚期非小细胞肺癌(NSCLC)患者总生存期的有益影响。在此,我们将分析扩展至在6个中心接受治疗的260例NSCLC患者。
在符合纳入标准的337例患者中,我们分析了260例每2周接受≥5次肽脉冲DC疫苗接种的患者。
从诊断开始的平均生存时间(MST)为33.0个月(95%置信区间[CI]:27.9 - 39.2),从首次接种疫苗开始的平均生存时间为13.8个月(95% CI 11.4 - 16.8)。注射部位直径≥30 mm的红斑反应与首次接种疫苗后的总生存期相关性最强(≥30 vs. <30 mm:MST 20.4 vs. 8.8个月,P < 0.001)。我们在之前对晚期胰腺癌患者的分析中报告了类似的发现。有趣的是,尽管腺癌患者和其他亚型患者之间都有此类发现,但前一组患者的总生存期显著延长,红斑反应率更高(分别为56.3%和37.3%,P = 0.014)。
这是第一项多中心研究,提示DC疫苗对晚期NSCLC患者,尤其是腺癌患者可能具有临床益处。这些发现提示了DC疫苗的一个特定潜在反应人群,值得在严格控制的前瞻性随机试验中进一步研究。