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, Cools, Nathalie, Nijs, Griet, Stein, Barbara, Lion, Eva, Van Driessche, Ann, Vandenbosch, Irma, Verlinden, Anke, Gadisseur, Alain P., Schroyens, Wilfried A., Muylle, Ludo, Vermeulen, Katrien, Maes, Marie-Berthe, Deiteren, Kathleen, Malfait, Ronald, Gostick, Emma, Lammens, Martin, Couttenye, Marie M., Jorens, Philippe, Goossens, Herman, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Oka, Yoshihiro, Fujiki, Fumihiro, Oji, Yusuke, Sugiyama, Haruo and Berneman, Zwi N. 2017. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood 130 (15) , pp. 1713-1721. 10.1182/blood-2017-04-780155

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Abstract

Relapse is a major problem in acute myeloid leukemia (AML) and adversely impacts survival. In this phase II study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms’ tumor 1 (WT1) mRNA as post-remission treatment in 30 AML patients at very high risk of relapse. There was a demonstrable anti-leukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which are 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 non-responders (53.8% vs. 25.0%; P=0.01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25% and the 5-year relapse-free survival was higher in responders than in non-responders (50% vs. 7.7%; P<0.0001). In patients ≤65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared to 51.7% and 18% in the Swedish Acute Leukemia Registry (SALR). Long-term clinical response was correlated with increased circulating frequencies of poly-epitope WT1-specific CD8+ T-cells. Long-term OS was correlated with interferon-γ+ and tumor necrosis factor-α+ WT1-specific responses in delayed type hypersensitivity-infiltrating CD8+ T-lymphocytes. In conclusion, vaccination of AML patients 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+ T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	American Society of Hematology
ISSN:	0006-4971
Date of First Compliant Deposit:	31 October 2017
Date of Acceptance:	1 August 2017
Last Modified:	05 Dec 2024 07:30
URI:	https://orca.cardiff.ac.uk/id/eprint/106076

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