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

Stroh, Jacob; Seckinger, Anja; Heider, Michael; Rudelius, Martina; Eichner, Ruth; Schick, Markus; Slawska, Jolanta; Emde-Rajaratnam, Martina; Salwender, Hans; Bertsch, Uta; Goldschmidt, Hartmut; Weisel, Katja; Scheid, Christof; Keller, Ulrich; Hose, Dirk und Bassermann, Florian (2022): MCT1 is a predictive marker for lenalidomide maintenance therapy in multiple myeloma. In: Blood Advances, Bd. 6, Nr. 2: S. 515-520

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2473-9529
• Sprache: Englisch