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

Anguille, Sébastien; Van De Velde, Ann L.; Smits, Evelien L.; Van Tendeloo, Viggo F.; Juliusson, Gunnar LU ; Cools, Nathalie; Nijs, Griet; Stein, Barbara; Lion, Eva and Driessche, Ann Van, et al. (2017) In Blood 130(15). p.1713-1721
Abstract

Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs... (More)

Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age £65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD81 T cells. Long-term OS was correlated with interferon-g1 and tumor necrosis factor-a1 WT1-specific responses in delayed-type hypersensitivity-infiltrating CD81 T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD81 T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.

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@article{99331fc5-8b3d-4584-bcdd-47392414fe4c,
  abstract     = {<p>Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P 5 .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P &lt; .0001). In patients age £65 and &gt;65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8<sup>1</sup> T cells. Long-term OS was correlated with interferon-g<sup>1</sup> and tumor necrosis factor-a<sup>1</sup> WT1-specific responses      in delayed-type      hypersensitivity-infiltrating CD8<sup>1</sup> T lymphocytes. In conclusion,      vaccination      of patients with AML with WT1 mRNA-electroporated DCs can be an effective      strategy      to prevent or delay relapse after standard chemotherapy, translating into      improved      OS rates, which are correlated with the induction of WT1-specific CD8<sup>1</sup> T-cell      response.      This trial was registered at www.clinicaltrials.gov as #NCT00965224.</p>},
  author       = {Anguille, Sébastien and Van De Velde, Ann L. and Smits, Evelien L. and Van Tendeloo, Viggo F. and Juliusson, Gunnar and Cools, Nathalie and Nijs, Griet and Stein, Barbara and Lion, Eva and Driessche, Ann Van and Vandenbosch, Irma and Verlinden, Anke and Gadisseur, Alain P. and Schroyens, Wilfried A. and Muylle, Ludo and Vermeulen, Katrien and Maes, Marie Berthe and Deiteren, Kathleen and Malfait, Ronald and Gostick, Emma and Lammens, Martin and Couttenye, Marie M. and Jorens, Philippe and Goossens, Herman and Price, David A. and Ladell, Kristin and Oka, Yoshihiro and Fujiki, Fumihiro and Oji, Yusuke and Sugiyama, Haruo and Berneman, Zwi N.},
  issn         = {0006-4971},
  language     = {eng},
  month        = {10},
  number       = {15},
  pages        = {1713--1721},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia},
  url          = {http://dx.doi.org/10.1182/blood-2017-04-780155},
  volume       = {130},
  year         = {2017},
}