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@ARTICLE{Heitmann:278585,
      author       = {J. S. Heitmann$^*$ and R. F. Schlenk$^*$ and D. Dörfel$^*$
                      and S. Kayser and K. Döhner and M. Heuser and F. Thol and
                      S. Kapp-Schwoerer and J. Labrenz and D. Edelmann$^*$ and M.
                      Märklin$^*$ and W. Vogel and W. Bethge and J. S. Walz$^*$
                      and L. Große-Hovest and M. Steiner and G. Jung$^*$ and H.
                      R. Salih$^*$},
      title        = {{P}hase {I} study evaluating the {F}c-optimized {FLT}3
                      antibody {FLYSYN} in {AML} patients with measurable residual
                      disease.},
      journal      = {Journal of hematology $\&$ oncology},
      volume       = {16},
      number       = {1},
      issn         = {1756-8722},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DKFZ-2023-01666},
      pages        = {96},
      year         = {2023},
      abstract     = {About half of AML patients achieving complete remission
                      (CR) display measurable residual disease (MRD) and
                      eventually relapse. FLYSYN is an Fc-optimized antibody for
                      eradication of MRD directed to FLT3/CD135, which is
                      abundantly expressed on AML cells.This first-in-human,
                      open-label, single-arm, multicenter trial included AML
                      patients in CR with persisting or increasing MRD and
                      evaluated safety/tolerability, pharmacokinetics and
                      preliminary efficacy of FLYSYN at different dose levels
                      administered intravenously (cohort 1-5: single dose of 0.5
                      mg/m2, 1.5 mg/m2, 5 mg/m2, 15 mg/m2, 45 mg/m2; cohort 6: 15
                      mg/m2 on day 1, 15 and 29). Three patients were treated per
                      cohort except for cohorts 4 and 6, which were expanded to
                      nine and ten patients, respectively. Primary objective was
                      safety, and secondary efficacy objective was ≥ 1 log MRD
                      reduction or negativity in bone marrow.Overall, 31 patients
                      were treated, of whom seven patients $(22.6\%)$ experienced
                      a transient decrease in neutrophil count (two grade 3,
                      others ≤ grade 2). No infusion-related reaction or
                      dose-limiting toxicity was observed. Adverse events (AEs)
                      were mostly mild to moderate, with the most frequent AEs
                      being hematologic events and laboratory abnormalities.
                      Response per predefined criteria was documented in $35\%$ of
                      patients, and two patients maintained MRD negativity until
                      end of study. Application of 45 mg/m2 FLYSYN as single or
                      cumulative dose achieved objective responses in $46\%$ of
                      patients, whereas $28\%$ responded at lower doses.FLYSYN
                      monotherapy is safe and well-tolerated in AML patients with
                      MRD. Early efficacy data are promising and warrant further
                      evaluation in an up-coming phase II trial. Trial
                      registration This clinical is registered on
                      clinicaltrials.gov (NCT02789254).},
      keywords     = {AML (Other) / FLT3 (Other) / Fc-optimized antibody (Other)
                      / Immunotherapy (Other) / MRD (Other)},
      cin          = {W010 / C060 / TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)W010-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)TU01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37587502},
      doi          = {10.1186/s13045-023-01490-w},
      url          = {https://inrepo02.dkfz.de/record/278585},
}