WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies

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 to 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 anti-tumor potential against thymic malignancies. This article is protected by copyright. All rights reserved.

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