WT1 peptide‐based immunotherapy for advanced thymic epithelial malignancies. Issue 11 (21st January 2018)

• Record Type: Journal Article
• Authors: Oji, Yusuke; Inoue, Masayoshi; Takeda, Yoshito; Hosen, Naoki; Shintani, Yasushi; Kawakami, Manabu; Harada, Takuya; Murakami, Yui; Iwai, Miki; Fukuda, Mari; Nishida, Sumiyuki; Nakata, Jun; Nakae, Yoshiki; Takashima, Satoshi; Shirakata, Toshiaki; Nakajima, Hiroko; Hasegawa, Kana; Kida, Hiroshi; Kijima, Takashi; Morimoto, Soyoko; Fujiki, Fumihiro; Tsuboi, Akihiro; Morii, Eiichi; Morita, Satoshi; Sakamoto, Junichi; Kumanogoh, Atsushi; Oka, Yoshihiro; Okumura, Meinoshin; Sugiyama, Haruo
• Is Part Of: International journal of cancer. Volume 142:Issue 11(2018)
• Page Start: 2375
• Page End: 2382
• Publication Date: 2018-01-21
• Subjects: thymic carcinoma -- thymoma -- WT1 -- WT1 peptide vaccine; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31253
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Thymic epithelial tumors are rare malignancies, and no optimal therapeutic regimen has been defined for patients with advanced disease. Patients with advanced thymic epithelial tumors, which were resistant or intolerable to prior therapies, were eligible for this study. Patients received 9 mer‐WT1‐derived peptide emulsified with Montanide ISA51 adjuvant via intradermal administration once a week as a monotherapy. After the 3‐month‐protocol treatment, the treatment was continued mostly at intervals of 2–4 weeks until disease progression or intolerable adverse events occurred. Of the 15 patients enrolled, 11 had thymic carcinoma (TC) and 4 had invasive thymoma (IT). Median period from diagnosis to the start of treatment was 13.3 and 65.5 months for TC and IT, respectively. No patients achieved a complete or partial response. Of the 8 evaluable TC patients, 6 (75.0%) had stable disease (SD) and 2 had progressive disease (PD). Of the 4 evaluable IT patients, 3 (75.0%) had SD and 1 (25.0%) had PD. Median period of monotherapy treatment was 133 and 683 days in TC and IT patients, respectively. No severe adverse events occurred during the 3‐month‐protocol treatment. As adverse events in long responders, thymoma‐related autoimmune complications, pure red cell aplasia and myasthenia gravis occurred in two IT patients. Cerebellar hemorrhage developed in a TC patient complicated with Von Willebrand disease. Induction of WT1‐specific immune responses was observed in the majority of the patients. WT1 peptide vaccine immunotherapy may have antitumor potential against thymic malignancies. Abstract : What's new? Because it is overexpressed in many types of cancer, the protein WT1 is a promising target for cancer immunotherapy. In this phase II clinical trial in advanced thymic cancers, the authors tested the efficacy of vaccinating patients with a WT1 peptide. While this did not shrink the tumors, 75% of patients maintained stable disease over several months. Because thymic tumors often go undetected until an advanced stage, WT1 immunotherapy may offer a useful adjunct approach in these difficult cancers.