Non-coding RNAs as predictive factors of oncological outcomes in plasma cell myeloma

Plasma cell myeloma (PCM) is the second most common haematological malignancy and accounts for 1% of all hematological tumors. PCM remains a challenging disease to treat because of its heterogeneity. Despite therapeutic advances, a significant proportion of patients do not respond to treatment or develop resistance, highlighting the need to identify reliable predictive biomarkers. Recent research suggests that non-coding RNAs (ncRNAs), i.e., microRNA (miRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA) are important regulators of gene expression and play a key role in the pathogenesis. Epigenetic changes precede genetic and protein modifications, and the analysis of a single ncRNA can reflect the status of several genes. Moreover, ncRNAs are stable and can be detected in a minimally invasive manner using readily available biological samples. This review synthesizes current preclinical and clinical data on ncRNAs as predictive biomarkers of response to PCM therapies, identifies the most promising molecules and their mechanisms of action, highlights key methodological limitations, and proposes a translational validation framework necessary for clinical implementation. The most promising candidates are miR-21, lncRNA: MALAT1, and PCAT-1, which are well established in the literature and confirmed at both the mechanistic and clinical levels. However, small cohorts, heterogeneity of studies, and lack of methodological standardization limit the strength of this evidence, highlighting the need for prospective multicenter studies with standardized analytical procedures.