Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia

mDC / mDC WT1

mDC / mDC WT1

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Summary

This study investigates the effect of dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment for patients with acute myeloid leukemia (AML) . The findings suggest the treatment is an effective strategy to prevent or delay relapse after standard chemotherapy.

Patients characteristics

30 patients with AML at very high risk of relapse after chemotherapy. Patients were 15 men and 15 women, with a median age at diagnosis of 65 years. Before WT1/DC vaccination, 27 patients had achieved complete remission (CR) after chemotherapy, whereas 3 had partial remission (PR).

Treatment

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.

Results

Clinical response
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.
Survival
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).
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Conclusion

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.

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Scientific article publishing date 1/8/2017

Immucura identifier BSC21_028EN

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