Upregulated Expression of ERBB2/HER2 in Multiple Myeloma as a Predictor of Poor Survival Outcomes

Abstract

The main goal of the present study was to examine if the RNA-sequencing (RNAseq)-based ERBB2/HER2 expression level in malignant plasma cells from multiple myeloma (MM) patients has clinical significance for treatment outcomes and survival. We examined the relationship between the RNAseq-based ERBB2 messenger ribonucleic acid (mRNA) levels in malignant plasma cells and survival outcomes in 787 MM patients treated on contemporary standard regimens. ERBB2 was expressed at significantly higher levels than ERBB1 as well as ERBB3 across all three stages of the disease. Upregulated expression of ERBB2 mRNA in MM cells was correlated with amplified expression of mRNAs for transcription factors (TF) that recognize the ERBB2 gene promoter sites. Patients with higher levels of ERBB2 mRNA in their malignant plasma cells experienced significantly increased cancer mortality, shorter progression-free survival, and worse overall survival than other patients. The adverse impact of high ERBB2 expression on patient survival outcomes remained significant in multivariate Cox proportional hazards models that accounted for the effects of other prognostic factors. To the best of our knowledge, this is the first demonstration of an adverse prognostic impact of high-level ERBB2 expression in MM patients. Our results encourage further evaluation of the prognostic significance of high-level ERBB2 mRNA expression and the clinical potential of ERBB2-targeting therapeutics as personalized medicines to overcome cancer drug resistance in high-risk as well as relapsed/refractory MM.

Phase II study of nivolumab in patients with genetic alterations in DNA damage repair and response who progressed after standard treatment for metastatic solid cancers (KM-06)

“…The notable increase in the ERBB2/3 signal in responders could be interpreted based on our trial population, which had a large proportion of patients with colorectal cancer. ERBB2 expression has been acknowledged as a poor prognostic marker 30 and is associated with reduced T-cell infiltration. 31 32 A recent study reported that ERBB2/3 mutated colorectal cancers are associated with increased MSI-H, TMB-H, and KRAS mutations compared with ERBB2/3 wild-type tumors.…”