Vaccination with dendritic cells (DCs) electroporated with Wilms’ tumour 1 (WT1) messenger RNA (mRNA) as post remission treatment. WT1 mRNA-electroporated DC (WT1/DC) vaccines were prepared and administered intradermally.
There was a demonstrable antileukemic effect of the WT1/DC vaccination only without any concomitant chemotherapy in 13 of 30 patients, corresponding to a clinical response rate of 43%. Of these 13 patients, 9 went into MR, as demonstrated by the normalization of WT1 transcript levels in blood and/or bone marrow. Of these 9 patients, 2 went from PR to CR and 5 were still in CR with a median duration of 114.5 months and median follow-up after the first WT1/DC vaccination of 109.4 months. Four patients relapsed after reaching MR, with 3 ultimately dying as a result of AML and 1 achieving long-term CR after undergoing allo-HSCT. In all relapsing patients, recurrence of AML was preceded and accompanied by increased WT1 transcript levels. In the remaining 4 patients, clinical response was characterized by SD, as demonstrated by elevated but stable WT1 transcript levels in blood and stable blood values without blasts.
The clinical response rate was 50% in patients with favorable cytogenetic risk. Among the 22- treatment response–evaluable patients with intermediate cytogenetic risk, 6 experienced an MR and 4 achieved SD, corresponding to a clinical response rate of 45%.
Overall, 6 of 30 patients had not yet relapsed and were still in first CR (CR1), with a median duration of 107.6 months and median follow-up of 101.8 months after the first dose of WT1/DCs. Of the remaining 24 of 30 patients, 1 did not reach CR1, 1 died presumably as a result of a lung adenocarcinoma without morphological evidence of AML relapse, 3 had a second or third relapse, and 19 had a first relapse. Four of these 19 patients with AML in first relapse received supportive care, whereas the remaining 15 were treated with salvage therapy (chemotherapy ±allo-HSCT). The CR2 rate in this group was 73.3% (11 of 15 patients); the remaining 4 patients had progressive disease.
11 of 30 patients were alive in CR, with a median OS from diagnosis of 99.4 months (range, 72.6- 125.5 months). Of these 11 patients, 6 were alive in continuing CR1. Five other surviving patients who relapsed after WT1/DC vaccination were brought back into CR by chemotherapy followed or not by allo-HSCT. Remarkably, 2 patients were alive in continuing CR respectively >7 and 4 years after achieving CR2 and CR3 with chemotherapy alone.
Of the 19 patients with AML who were in first relapse after WT1/DC vaccination, 52.6% were alive at 3 years and 36.8% at 5 years from diagnosis. Of the latter patients, 4 achieved CR2 after chemotherapy, and the other 3 had a remarkably long period of CR1 before relapsing (47, 51.6, and 59.8 months after the start of WT1/DC vaccination).
In summary, WT1-targeted DC vaccination can elicit antileukemia T-cell immunity in patients with AML at very high risk of relapse. The induction of functional WT1-specific CD81 T cells is likely a mechanism to help eliminate residual leukemic cells, decrease the likelihood of AML relapse, and improve survival. Vaccination with WT1/DCs can therefore be considered as a nontoxic, post remission strategy to prevent or delay relapse of AML in the adjuvant setting.