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

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). Patientswith high expression levels of MCT1 showed significantly reduced PFS (31.9months vs 48.2months in MCT1high vs MCT1low; P=.03) and OS (75.9months vs not reached [NR] in MCT1high vs MCT1low; P=.001) in cases with lenalidomidemaintenance, whereas MCT1 expression had no significant impact on PFS or OS in caseswith bortezomibmaintenance.We validated the predictive role of MCT1 for IMiD-based maintenance in an independent cohort of patients who received thalidomide (OS, 83.6months vs NR in MCT1high vs MCT1low; P=.03). Functional validation showed thatMCT1 overexpression in humanMMcell lines significantly reduced the efficacy of lenalidomide, whereas no change was observedwith bortezomib treatment, either in vitro or in aMMxenograftmodel. Our findings have established MCT1 expression as a predictivemarker for response to lenalidomide-basedmaintenance in patients withMM.