Can Protein Expression Predict Response to Combination Therapy for Multiple Myeloma?
Posted: Tuesday, February 9, 2021
María-Victoria Mateos, MD, PhD, of the University Hospital of Salamanca, Spain, and colleagues have identified biomarkers that may help predict outcomes in patients with multiple myeloma treated with a three-drug combination: bortezomib, lenalidomide, and dexamethasone. The study, published in Blood Advances, evaluated the levels of proteins involved in the mechanism of action of the drugs. They found that high levels of Ikaros and PSMD10 and low levels of IRF4 proteins are associated with shorter survival in patients treated with the triplet.
The study included samples from 174 patients with newly diagnosed multiple myeloma who were enrolled in the Spanish Myeloma group clinical trial, GEM2012. The levels of 12 proteins were quantified by capillary nanoimmunoassay in CD138-purified samples.
A total of three of the five proteins involved in the mechanism of action of bortezomib—PSMD1, PSMD4, and PSMD10—negatively influenced survival. Of the five analyzed proteins involved in lenalidomide’s mode of action, low levels of cereblon and IRF4 protein and high levels of Ikaros, AGO2, and Aiolos were significantly associated with a shorter time to disease progression. Although the glucocorticoid receptor level in itself had no significant impact on prognosis in these patients, a high ratio of exportin 1 to glucocorticoid was associated with a shorter time to disease progression and progression-free survival.
Additionally, the multivariate Cox model identified high levels of PSMD10 and Ikaros, low levels of IRF4 protein expression, and the presence of high-risk cytogenetics as independently associated with a shorter time to disease progression and progression-free survival.
“These results highlight the value of assessing proteins related to the mechanism of action of drugs used in multiple myeloma for predicting treatment outcome,” concluded the authors.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.