Posted: Wednesday, March 23, 2022
An article published in Blood Advances addressed whether specific genetic markers could predict the efficacy of immunomodulatory treatment in patients with multiple myeloma (MM). Florian Bassermann, MD, PhD, of Technical University of Munich, and colleagues conducted gene-expression profiling and RNA sequencing studies to examine which genetic markers might have the highest correlation with progression-free and overall survival in patients with multiple myeloma. Their findings revealed that patients with high expression levels of MCT1 had reduced progression-free and overall survival, especially in cases with lenalidomide maintenance. Functional validation studies also revealed that overexpression of MCT1 in human myeloma cell lines significantly reduced the efficacy of lenalidomide.
“Biomarkers that predict response to lenalidomide maintenance therapy in patients with…MM…have remained elusive. We have shown that immunomodulatory drugs…exert anti-MM activity via destabilization of MCT1 and CD147…. [Following investigations], our findings have established MCT1 expression as a predictive marker for response to lenalidomide-based maintenance,” stated Dr. Bassermann and colleagues.
Gene-expression profiling was performed on a total of 1,486 patients with multiple myeloma. Of them, 654 received high-dose melphalan and autologous stem cell transplantation and maintenance with bortezomib (n = 101), thalidomide (n = 98), or lenalidomide (n = 455) as the first-line treatment. Statistical analyses were used to determine the correlation of CD147 and MCT1 with progression-free and overall survival. Xenograft models were then used to examine whether the efficacy of immunomodulatory drugs was affected by overexpression of specific genetic markers.
Overall findings revealed that patients with high expression levels of MCT1 who received lenalidomide maintenance had significantly reduced progression-free survival compared with those who had low MCT1 levels (31.9 months vs. 48.2 months ; P = .03) and overall survival (75.9 months vs. not reached; P = .001). Functional validation also revealed that MCT1 overexpression significantly reduced the efficacy of lenalidomide, highlighting it as a predictive marker for immunomodulatory treatments.
Disclosure: For full disclosures of the study authors visit, ashpublications.org.