Toru Kiguchi1, Masaki Yamaguchi2, Naoki Takezako3, Shuichi Miyawaki4, Koichi Masui5, Yuichiro Ihara6, Masao Hirota7, Naoko Shimofurutani5, Tomoki Naoe8. 1. Chugoku Central Hospital, Fukuyama, Japan. kiguchi-t@umin.ac.jp. 2. Ishikawa Prefectural Central Hospital, Kanazawa, Japan. 3. National Hospital Organization Disaster Medical Center of Japan, Tokyo, Japan. 4. Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan. 5. Otsuka Pharmaceutical Co., Ltd, Osaka, Japan. 6. Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan. 7. Otsuka Pharmaceutical Co., Ltd, Tokyo, Japan. 8. National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
Abstract
PURPOSE: Complete remission (CR) of acute myeloid leukemia (AML) in elderly patients has a short duration, and there is no suitable post-remission therapy. We explored the role of the Wilms' tumor 1 helper peptide OCV-501 to prevent recurrence after remission. METHODS: This placebo-controlled phase 2 study was designed to evaluate accurately the efficacy and immunogenicity of OCV-501 in elderly AML patients. Elderly AML patients who achieved first CR were randomly allocated to receive either OCV-501 (N = 69) or placebo (N = 65) once a week for eight weeks and then every two weeks until week 104. The primary endpoint was disease-free survival (DFS). RESULTS: Nineteen (27.5%) patients in the OCV-501 group and 23 (35.4%) patients in the placebo group completed the study without relapse. The median DFS in the OCV-501 and placebo groups was 12.1 and 8.4 months, respectively (p = 0.7671, hazard ratio [95% confidence interval]: 0.933 [0.590, 1.477]). The major drug adverse reactions were injection-site reactions. Although treatment with OCV-501 did not prolong DFS for elderly AML patients, post hoc analysis found that immune responders to OCV-501 whose specific IgG was > 10,000 ng/mL (N = 16) and whose WT1-specific interferon-γ response was > 10 pg/mL (N = 26) had significantly longer overall survival compared with placebo. CONCLUSIONS: The placebo-controlled design of this study and quantitative immunological monitoring provides new insight into the relationship between peptide-induced immune responses and survival, suggesting future perspectives for cancer immunotherapy.
PURPOSE: Complete remission (CR) of acute myeloid leukemia (AML) in elderly patients has a short duration, and there is no suitable post-remission therapy. We explored the role of the Wilms' tumor 1 helper peptide OCV-501 to prevent recurrence after remission. METHODS: This placebo-controlled phase 2 study was designed to evaluate accurately the efficacy and immunogenicity of OCV-501 in elderly AML patients. Elderly AML patients who achieved first CR were randomly allocated to receive either OCV-501 (N = 69) or placebo (N = 65) once a week for eight weeks and then every two weeks until week 104. The primary endpoint was disease-free survival (DFS). RESULTS: Nineteen (27.5%) patients in the OCV-501 group and 23 (35.4%) patients in the placebo group completed the study without relapse. The median DFS in the OCV-501 and placebo groups was 12.1 and 8.4 months, respectively (p = 0.7671, hazard ratio [95% confidence interval]: 0.933 [0.590, 1.477]). The major drug adverse reactions were injection-site reactions. Although treatment with OCV-501 did not prolong DFS for elderly AML patients, post hoc analysis found that immune responders to OCV-501 whose specific IgG was > 10,000 ng/mL (N = 16) and whose WT1-specific interferon-γ response was > 10 pg/mL (N = 26) had significantly longer overall survival compared with placebo. CONCLUSIONS: The placebo-controlled design of this study and quantitative immunological monitoring provides new insight into the relationship between peptide-induced immune responses and survival, suggesting future perspectives for cancer immunotherapy.
Authors: K M Call; T Glaser; C Y Ito; A J Buckler; J Pelletier; D A Haber; E A Rose; A Kral; H Yeger; W H Lewis Journal: Cell Date: 1990-02-09 Impact factor: 41.582
Authors: Antonio Di Stasi; Antonio M Jimenez; Kentaro Minagawa; Mustafa Al-Obaidi; Katayoun Rezvani Journal: Front Immunol Date: 2015-02-04 Impact factor: 7.561