Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia

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  • Disha Malani
  • Ashwini Kumar
  • Oscar Brück
  • Mika Kontro
  • Bhagwan Yadav
  • Monica Hellesøy
  • Olli Dufva
  • Matti Kankainen
  • Samuli Eldfors
  • Swapnil Potdar
  • Jani Saarela
  • Laura Turunen
  • Alun Parsons
  • Imre Västrik
  • Katja Kivinen
  • Janna Saarela
  • Riikka Räty
  • Minna Lehto
  • Maija Wolf
  • Bjorn Tore Gjertsen
  • Satu Mustjoki
  • Tero Aittokallio
  • Caroline A. Heckman
  • Olli Kallioniemi
  • Kimmo Porkka

We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of patients with AML, and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five patients with AML to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled the identification of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3 inhibitors. Integration of molecular profiling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommen-dations, providing a paradigm for individualized implementation of functional precision cancer medicine.

OriginalsprogEngelsk
TidsskriftCancer Discovery
Vol/bind12
Udgave nummer2
Sider (fra-til)388-401
Antal sider14
ISSN2159-8274
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
We are most grateful to the patients and their families for participat-ing in the study. We thank the Academy of Finland grant, Academy of Finland Center of Excellence on Translational Cancer Biology, the iCAN Digital Precision Cancer Medicine Flagship, Sigrid Jus?lius Foundation, Cancer Society of Finland, Tekes/Business Finland Salwe program, HUS-EVO, and HUCS Institute for support to this study. We utilized FIMM/HiLife/Biocenter Finland local and national infrastructures (Genome-wide, Bioinformatics, and DDCB National infra-structures) as well as national networks for EU infrastructures BBMRI, ELIXIR, EATRIS, and EU-OPENSCREEN. We thank the excellent staff and resources provided by the FIMM Technology Centre and the FIMM High-Throughput Biomedicine Unit. We thank Minna Suvela, Alun Parsons, and Siv Knaappila for processing patient samples. The authors acknowledge the assistance and support of the personnel at the FIMM Sequencing Unit, especially Pekka Ellonen and Pirkko Mattila. The authors acknowledge the support of personnel at the FIMM High-Throughput Biomedicine Unit: Elina Huovari, Aleksandr Ianevski, Meri Kokkonen, Evgeny Kulesskiy, Sergey Kuznetsov, Karoliina Laamanen, Elina Lehtinen, Piia Mikkonen, Maria Nurmi, Katja N?rhi, Katja Suomi, and Sanna Timonen. D. Malani received personal funding support from the Finnish Cultural Foundation, Blood Disease Research Foundation, Finnish Hematology Association, K. Albin Johansson Foundation, Paivikki ja Sakari Sohlberg Foundation, Maud Kuistila Memorial Foundation, and Helsinki Biomedicum foundation to support this research. M. Helles?y and B.T. Gjertsen received funding from The Norwegian Cancer Society and Helse Vest Health Trust. A. Kumar received an EMBO short-term lab visit fellowship for this study. S. Mustjoki received funding from European Research Council (M-IMM project), Academy of Finland, Cancer Society of Finland, and Sigrid Jus?lius Foundation. T. Aittokallio received funding from Academy of Finland (grants 292611, 310507 and 313267), Cancer Society of Finland, and Sigrid Jus?lius Foundation. K. Wennerberg received funding from Novo Nordisk Foundation (Grant Number NNF17CC0027852). M. Kontro received a University of Helsinki Early Career Grant. C.A. Heckman received funding from the Sigrid Jus?lius Foundation, Cancer Society of Finland, and Academy of Finland (grants 1320185 and 334781). O. Kallioniemi received support from Academy of Finland (259777, 278741, 271845, and 333050), Cancer Society of Finland (120089, 140114, 160080, 170112, and 190116) and Sigrid Jus?lius Foundation, Knut and Alice Wallenberg Foundation (KAW; 2015.0291), Swedish Foundation for Strategic Research (SSF; SB16-0058), VR environment grant (2017-06095), and Vinnova (2018-03338).

Publisher Copyright:
© 2021 The Authors; Published by the American Association for Cancer Research.

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