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The anti-myeloma effects of the selective JAK1 inhibitor (INCB052793) alone and in combination in vitro and in vivo

  • Eric Sanchez
  • Mingjie Li
  • Saurabh Patil
  • Camilia M. Soof
  • Jason D. Nosrati
  • Remy E. Schlossberg
  • Aleksandra Vidisheva
  • Edward J. Tanenbaum
  • Tara Hekmati
  • Brian Zahab
  • Cathy Wang
  • George Tang
  • Haiming Chen
  • James R. BerensonEmail author
Original Article

Abstract

The Janus kinase (JAK) pathway has been shown to play key roles in the growth and resistance to drugs that develop in multiple myeloma (MM) patients. The anti-MM effects of the selective JAK1 inhibitor INCB052793 (INCB) alone and in combination with anti-MM agents were evaluated in vitro and in vivo. Significant inhibition of cell viability of primary MM cells obtained fresh from MM patients, and the MM cell lines RPMI8226 and U266, was observed with single agent INCB and was enhanced in combination with other anti-MM agents including proteasome inhibitors and glucocorticosteroids. Single-agent INCB resulted in decrease in tumor growth of the MM xenograft LAGκ-1A growing in severe combined immunodeficient mice. Mice dosed with INCB (30 mg/kg) showed significant reductions in tumor volume on days 28, 35, 42, 49, 56, and 63. Similarly, INCB at 10 mg/kg showed anti-tumor effects on days 56 and 63. Tumor-bearing mice receiving combinations of INCB with carfilzomib, bortezomib, dexamethasone, or lenalidomide showed significantly smaller tumors when compared to vehicle control and mice treated with single agents. These results provide further support for the clinical evaluation of INCB052793 alone and in combination treatment for MM patients.

Keywords

Multiple myeloma Janus kinase inhibitor Tumor In vivo Xenograft 

Notes

Acknowledgements

We gratefully acknowledge Tanya M. Spektor and Jenna Riehl for reviewing of the manuscript.

Funding information

JRB has received consulting fees, honoraria and research support for clinical and laboratory research from Incyte Corporation, whom also supported this study by research/study funding (INCY#24378).

Compliance with ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). All institutional and national guidelines for the care and use of laboratory animals were followed. Informed consent was obtained from all patients for being included in the study. All animal studies were conducted according to the protocols approved by the Institutional Animal Care and Use Committee (approval no. 13.006).

Conflict of interest

This research was supported by a grant from Incyte Corporation. J. Berenson is a consultant/advisory board member for Incyte Corporation.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Eric Sanchez
    • 1
  • Mingjie Li
    • 1
  • Saurabh Patil
    • 1
  • Camilia M. Soof
    • 1
  • Jason D. Nosrati
    • 2
  • Remy E. Schlossberg
    • 1
  • Aleksandra Vidisheva
    • 3
  • Edward J. Tanenbaum
    • 1
  • Tara Hekmati
    • 1
  • Brian Zahab
    • 1
  • Cathy Wang
    • 1
  • George Tang
    • 1
  • Haiming Chen
    • 1
  • James R. Berenson
    • 1
    Email author
  1. 1.Institute for Myeloma & Bone Cancer ResearchWest HollywoodUSA
  2. 2.College of Human MedicineMichigan State UniversityEast LansingUSA
  3. 3.College of MedicineUniversity of ArizonaTucsonUSA

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