MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma

Jacob Stroh, Anja Seckinger, Michael Heider, Martina Rudelius, Ruth Eichner, Markus Schick, Jolanta Slawska, Martina Emde-Rajaratnam, Hans Salwender, Uta Bertsch, Hartmut Goldschmidt, Katja Weisel, Christof Scheid, Ulrich Keller, Dirk Hose, Florian Bassermann

Onderzoeksoutput: Articlepeer review

Samenvatting

Biomarkers that predict response to lenalidomide maintenance therapy in patients with multiple myeloma (MM) have remained elusive. We have shown that immunomodulatory drugs (IMiDs) exert anti-MM activity via destabilization of MCT1 and CD147. In this study, cell samples of 654 patients with MM who received lenalidomide (n = 455), thalidomide (n = 98), or bortezomib (n = 101) maintenance were assessed by gene expression profiling and RNA sequencing, followed by correlation of MCT1 and CD147 expression with data for progression-free survival (PFS) and overall survival (OS). Patients with high expression levels of MCT1 showed significantly reduced PFS (31.9 months vs 48.2 months in MCT1high vs MCT1low; P = .03) and OS (75.9 months vs not reached [NR] in MCT1high vs MCT1low; P = .001) in cases with lenalidomide maintenance, whereas MCT1 expression had no significant impact on PFS or OS in cases with bortezomib maintenance. We validated the predictive role of MCT1 for IMiD-based maintenance in an independent cohort of patients who received thalidomide (OS, 83.6 months vs NR in MCT1high vs MCT1low; P = .03). Functional validation showed that MCT1 overexpression in human MM cell lines significantly reduced the efficacy of lenalidomide, whereas no change was observed with bortezomib treatment, either in vitro or in a MM xenograft model. Our findings have established MCT1 expression as a predictive marker for response to lenalidomide-based maintenance in patients with MM.

Originele taal-2English
Pagina's (van-tot)515-520
Aantal pagina's6
TijdschriftBlood Advances
Volume6
Nummer van het tijdschrift2
DOI's
StatusPublished - 25 jan 2022

Bibliografische nota

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Vingerafdruk

Duik in de onderzoeksthema's van 'MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma'. Samen vormen ze een unieke vingerafdruk.

Citeer dit