Phase 1/2 study of the WT 1 peptide cancer vaccine WT 4869 in patients with myelodysplastic syndrome

• Published in: Cancer science Vol. 108; no. 12; pp. 2445 - 2453
• Main Authors: Ueda, Yasunori, Ogura, Michinori, Miyakoshi, Shigesaburo, Suzuki, Takahiro, Heike, Yuji, Tagashira, Shuzo, Tsuchiya, Satoru, Ohyashiki, Kazuma, Miyazaki, Yasushi
• Format: Journal Article
• Language: English
• Published: Tokyo John Wiley & Sons, Inc 01.12.2017
• Subjects: Antigens; Blood transfusion; Bone marrow; Cancer therapies; Cancer vaccines; Creatine; Creatine kinase; Cytotoxicity; Disease control; Drug dosages; Erythrocytes; Fever; Hematology; Hemorrhage; Hospitals; Immunotherapy; Leukemia; Lymphocytes T; Medical prognosis; Medicine; Myelodysplastic syndrome; Neutropenia; Oncology; Patients; Peptides; Pharmaceuticals; Pneumonitis; Research funding; Vaccines; Japan
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13409

WT 4869 is a synthetic peptide vaccine derived from the Wilms’ tumor gene 1 ( WT 1) protein. This phase 1/2 open‐label study evaluated the safety and efficacy of WT 4869, and biomarkers for response, in patients with myelodysplastic syndrome. WT 4869 (5–1200 μg/dose) was administered intradermally every 2 weeks, according to a 3 + 3 dose‐escalation method in higher‐risk (International Prognostic Scoring System score ≥1.5) or lower‐risk (score <1.5) red blood cell transfusion‐dependent patients with myelodysplastic syndrome. Twenty‐six patients were enrolled and treated (median age, 75 years; range, 32 to 89). The most common adverse event was injection site reaction (61.5%). Main grade 3 or 4 adverse events were neutropenia (30.8%), febrile neutropenia, pneumonia, elevated blood creatine phosphokinase levels and hypoalbuminemia (all 7.7%). Dose‐limiting toxicities occurred in 1 patient in the 50 μg/dose cohort (pyrexia, muscle hemorrhage and hypoalbuminemia) and 1 patient in the 400 μg/dose cohort (pneumonitis); however, the maximum tolerated dose could not be determined from this trial. The overall response rate was 18.2%, the disease control rate was 59.1% and median overall survival was 64.71 weeks (95% confidence interval: 50.29, 142.86) as assessed by the Kaplan–Meier method. Subgroup analysis of azacitidine‐refractory patients with higher‐risk myelodysplastic syndrome (11 patients) showed median overall survival of 55.71 weeks (approximately 13 months). WT 1‐specific cytotoxic T lymphocyte induction was observed in 11 of 25 evaluable patients. WT 4869 was well tolerated in patients with myelodysplastic syndrome and preliminary data suggest that WT 4869 is efficacious. This trial was registered at www.clinicaltrials.jp as Japic CTI ‐101374.