Universität zu Köln

Stroh, Jacob, Seckinger, Anja, Heider, Michael, Rudelius, Martina, Eichner, Ruth ORCID: 0000-0002-8433-9452, Schick, Markus, Slawska, Jolanta, Emde-Rajaratnam, Martina, Salwender, Hans, Bertsch, Uta, Goldschmidt, Hartmut, Weisel, Katja, Scheid, Christof, Keller, Ulrich, Hose, Dirk and Bassermann, Florian (2022). MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma. Blood Adv., 6 (2). S. 515 - 521. AMSTERDAM: ELSEVIER. ISSN 2473-9537

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Stroh, Jacob UNSPECIFIED UNSPECIFIED UNSPECIFIED Seckinger, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Heider, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Rudelius, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichner, Ruth UNSPECIFIED orcid.org/0000-0002-8433-9452 UNSPECIFIED Schick, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Slawska, Jolanta UNSPECIFIED UNSPECIFIED UNSPECIFIED Emde-Rajaratnam, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Salwender, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Bertsch, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Goldschmidt, Hartmut UNSPECIFIED UNSPECIFIED UNSPECIFIED Weisel, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheid, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Keller, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Hose, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Bassermann, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-694509
DOI:	10.1182/bloodadvances.2021005532.
Journal or Publication Title:	Blood Adv.
Volume:	6
Number:	2
Page Range:	S. 515 - 521
Date:	2022
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2473-9537
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STEM-CELL TRANSPLANTATION; CD147; EXPRESSION; TRANSPORTERS; PROMOTES; AXIS Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69450