WT1 peptide vaccines of post-allogeneic HSCT maintenance immunotherapy for pediatric acute leukemias: a phase 2 study.

This phase 2 clinical study evaluated the efficacy and safety of post-allogeneic hematopoietic stem cell transplantation maintenance cancer immunotherapy using 2 Wilms tumor 1 (WT1) peptide vaccines, MCI, for pediatric refractory acute leukemias. Each of 17 patients (median age, 8.3 years [range, 2-18]) was intradermally injected with either of the vaccines. The 3-year overall survival (OS) rate (primary end point) was 70.6% (95% confidence interval [CI], 43.1-86.6); this rate was >30%, a historical control benchmark, and was attributable to the fact that 12 clinical responders, who sustained complete remission at year 1 after the initiation of vaccination, had a high 3-year OS rate of 91.7% (95% CI, 53.9-98.7). WT1-specific cytotoxic T-cell (CTL) frequency in peripheral blood (PB) from all 12 clinical responders increased significantly after vaccination, reaching the maximum by week 12 of vaccination (before, 0.25% ± 0.08%; after, 1.07% ± 0.24%; P< .001), whereas WT1-specific CTL frequency in PB from clinical nonresponders remained unchanged after vaccination (before, 0.12% ± 0.2%; after, 0.20% ± 0.25%; P = .424). The estimated 3-year OS rate was significantly higher for 11 immune responders (who showed a ≥1.455-fold increase from the baseline value: 90.9%) than for 5 immune nonresponders (40.0%; P = .027). Elevated WT1-specific CTL frequency in the PB before vaccination predicted the subsequent favorable patient prognosis. No patient discontinued treatment because of MCI. Adverse events including graft-versus-host disease were manageable. MCI was suggested to be very effective and safe for pediatric patients with refractory acute leukemias, indicating its potential to improve their survival through relapse prevention. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as #UMIN000005319.