Efficacy and safety of Wilms' tumor 1 helper peptide OCV-501 in elderly patients with acute myeloid leukemia: a multicenter, randomized, double-blind, placebo-controlled phase 2 trial.

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.

• Authors: Toru Kiguchi, Masaki Yamaguchi, Naoki Takezako, Shuichi Miyawaki, Koichi Masui, Yuichiro Ihara, Masao Hirota, Naoko Shimofurutani, Tomoki Naoe
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 71 Issue 6 Pg. 1419-1430 (Jun 2022) ISSN: 1432-0851 [Electronic] Germany
• PMID: 34677647 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chemical References

• Peptides
• WT1 Proteins

Topics

• Aged
• Disease-Free Survival
• Humans
• Leukemia, Myeloid, Acute
• Peptides
• Remission Induction
• WT1 Proteins