Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond

Phaik Ju Teoh; Mun Yee Koh; Constantine Mitsiades; Sarah Gooding; Wee Joo Chng

doi:10.3324/haematol.2024.285636

Haematologica (Nov 2024)

Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond

Phaik Ju Teoh,
Mun Yee Koh,
Constantine Mitsiades,
Sarah Gooding,
Wee Joo Chng

Affiliations

Phaik Ju Teoh: Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Division of Molecular and Cellular Oncology (MCO), Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, 02142
Mun Yee Koh: Cancer Science Institute of Singapore, National University of Singapore, 117599
Constantine Mitsiades: Division of Molecular and Cellular Oncology (MCO), Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA; Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, 02142
Sarah Gooding: Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, OX3 7LE, UK; Oxford Centre for Translational Myeloma Research, University of Oxford, Oxford, OX1 2JD, UK; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS
Wee Joo Chng: Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Division of Haematology, Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Health System, 119228

DOI: https://doi.org/10.3324/haematol.2024.285636
Journal volume & issue: Vol. 999, no. 1

Abstract

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Acquired resistance to immunomodulatory drugs (IMiDs) remains a significant unmet need in the treatment landscape of multiple myeloma (MM). CRBN pathway-dependent mechanisms are known to be vital contributors to IMiD resistance; however, they may account for only a small proportion. Recent research has unveiled additional mechanisms of acquired IMiD resistance that are independent of the CRBN pathway. In this review, we provide a comprehensive overview of the existing work on IMiD resistance in MM, focusing specifically on the emerging evidence of CRBN pathway-independent mechanisms. Finally, we discuss the plausible actionable strategies and outlook for IMiD-based therapies moving forward.

Published in Haematologica

ISSN: 0390-6078 (Print); 1592-8721 (Online)
Publisher: Ferrata Storti Foundation
Country of publisher: Italy
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the blood and blood-forming organs
Website: http://www.haematologica.org

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