Hidenori Takahashi1,2,3, Shigetaka Shimodaira4, Masahiro Ogasawara5, Shuichi Ota5, Masanori Kobayashi6, Hirofumi Abe7, Yuji Morita8, Kazuhiro Nagai9, Shunichi Tsujitani10, Masato Okamoto11, Yukio Suzuki12, Yoichi Nakanishi1, Yoshikazu Yonemitsu13. 1. Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan. 2. R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. 3. Seren Clinic Fukuoka, Fukuoka, 810-0001, Japan. 4. Cell Processing Center, Shinshu University Hospital, Matsumoto, Nagano, 390-8621, Japan. 5. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Hokkaido, 003-0006, Japan. 6. Seren Clinic Nagoya, Nagoya, Aichi, 460-0008, Japan. 7. Seren Clinic Kobe, Kobe, Hyogo, 650-0001, Japan. 8. Seren Clinic Tokyo, Tokyo, 108-0071, Japan. 9. Transfusion and Cell Therapy Unit, Nagasaki University Hospital, Nagasaki, 852-8501, Japan. 10. Tottori University Hospital Cancer Center, Tottori, Yonago, 683-8504, Japan. 11. Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo, 108-8641, Japan. 12. Division of Clinical Medicine, Research and Education Center for Clinical Pharmacy, Kitasato University School of Pharmacy, Tokyo, 108-8641, Japan. 13. R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. yonemitu@med.kyushu-u.ac.jp.
Abstract
OBJECTIVE: 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. METHODS: Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVE: 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. METHODS: Of the 337 patients who met the inclusion criteria, we analyzed 260 patients who received ≥5 peptide-pulsed DC vaccinations once every 2 weeks. RESULTS: 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). CONCLUSIONS: 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.
Authors: Iris A E van der Hoorn; Georgina Flórez-Grau; Michel M van den Heuvel; I Jolanda M de Vries; Berber Piet Journal: Front Immunol Date: 2021-06-28 Impact factor: 7.561