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ACUTE MYELOID LEUKEMIA

WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy

Leukemia volume 37, pages 1842–1849 (2023)Cite this article

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Abstract

Intensive induction chemotherapy achieves complete remissions (CR) in >60% of patients with acute myeloid leukemia (AML) but overall survival (OS) is poor for relapsing patients not eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Oral azacytidine may be used as maintenance treatment in AML in first remission, but can be associated with substantial side effects, and less toxic strategies should be explored. Twenty AML patients in first CR (CR1) ineligible for allo-HSCT were treated with FDC101, an autologous RNA-loaded mature dendritic cell (mDC) vaccine expressing two leukemia-associated antigens (LAAs). Each dose consisted of 2.5–5 × 106 mDCs per antigen, given weekly until week 4, at week 6, and then monthly, during the 2-year study period. Patients were followed for safety and long-term survival. Treatment was well tolerated, with mild and transient injection site reactions. Eleven of 20 patients (55%) remained in CR, while 4 of 6 relapsing patients achieved CR2 after salvage therapy and underwent allo-HSCT. OS at five years was 75% (95% CI: 50–89), with 70% of patients ≥60 years of age being long-term survivors. Maintenance therapy with this DC vaccine was well tolerated in AML patients in CR1 and was accompanied by encouraging 5-year long-term survival.

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Fig. 1: Swimmer plot illustrating long-term outcomes of patients treated with DC vaccines.
Fig. 2: Quality analysis of DC vaccine sub-batches.
Fig. 3: The effect of WT1 and PRAME vaccination on the immune system.
Fig. 4: Gene expression levels of WT1 and PRAME.

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Data availability

Data are available upon request from the authors at their discretion.

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Authors and Affiliations

  1. Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway

    Yngvar Fløisand

  2. Department of Hematology, Oslo University Hospital, Oslo, Norway

    Mats Remberger

  3. Clinical Research and Development Unit, Uppsala University Hospital, Uppsala, Sweden

    Mats Remberger

  4. Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway

    Iris Bigalke, Dag Josefsen, Else Marit Inderberg, Richard W. Olaussen & Gunnar Kvalheim

  5. Department of Pathology, Oslo University Hospital, Oslo, Norway

    Helen Vålerhaugen

  6. Department of Clinical Science, University of Bergen; Department of Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway

    Bjørn Tore Gjertsen

  7. Medigene Immunotherapies GmbH and Medigene AG, Martinsried, Germany

    Rene Goedkoop, Christiane Geiger, Petra U. Prinz, Frauke M. Schnorfeil, Kai Pinkernell & Dolores J. Schendel

  8. Bavarian Nordic GmbH, Martinsried, Germany

    Frauke M. Schnorfeil

  9. Dr. Falk Pharma, Freiburg, Germany

    Kai Pinkernell

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  1. Yngvar Fløisand
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Contributions

YF, GK, DS wrote the protocol. YF, GK, DJ, RWO, HV, IB contributed patient and treatment data for analysis. RG, CG, KP, PUP, FMS, DS collected data and undertook statistical analysis. YF, GK, DS, RG reviewed the data and prepared the manuscript. All authors reviewed the analysis results and edited the manuscript.

Corresponding author

Correspondence to Yngvar Fløisand.

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Competing interests

CG, PP, and DJS are employees of Medigene Immunotherapies GmbH/Medigene AG which hold commercial interests in DC vaccines and served as Sponsor of this study. KP and FMS are previous employees of Medigene Immunotherapies GmbH/Medigene AG and RG is a consultant to Medigene AG.

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Fløisand, Y., Remberger, M., Bigalke, I. et al. WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy. Leukemia 37, 1842–1849 (2023). https://doi.org/10.1038/s41375-023-01980-3

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  • DOI: https://doi.org/10.1038/s41375-023-01980-3

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