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

This phase II clinical study evaluated the efficacy and safety of post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) maintenance cancer immunotherapy using two WT1 peptide vaccines-MCI-for pediatric refractory acute leukemias. Each of 17 patients (median age, 8.3 years; age range, 2-18 years) was intradermally injected with either of the vaccines. The 3-year overall survival (OS) rate-the primary endpoint-was 70.6% [95% confidence interval (CI), 43.1-86.6%]; this rate was higher than 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 of 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), while 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 ³1.455-fold increase from the baseline value: 90.9%) than for 5 immune nonresponders (40.0%; P=.027). Elevated WT1-specific CTL frequency in PB before vaccination predicted the subsequent favorable prognosis of all patients. No patients discontinued treatment due to 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. UMIN000005319