Multiple Myeloma in the Era of Precision Medicine: Recent Advances in Pathogenesis, Diagnosis, and Treatment

Background: Multiple myeloma (MM) is the second most common hematologic malignancy worldwide, with rising incidence due to population aging and improved recognition of precursor conditions such as MGUS and SMM. Despite significant therapeutic advances, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies, MM remains incurable, highlighting the need for continued research into novel diagnostics and treatment strategies. Aims: The aim of this review is to critically analyze recent advances in molecular diagnostics, minimal residual disease monitoring, and immunotherapeutic strategies in multiple myeloma, with emphasis on their clinical applicability and future perspectives. Methods: A narrative review of the English-language literature (2020–2025) was conducted in PubMed and Google Scholar. Eligible studies included clinical trials, systematic reviews, meta-analyses, observational studies, and international guidelines involving adult patients (≥19 years). Articles addressing molecular diagnostics, novel biomarkers (e.g., ctDNA, serum BCMA), or systemic therapies (including proteasome inhibitors, CAR-T cells, and bispecific antibodies) were considered. Priority was given to randomized phase II/III trials, real-world evidence, guidelines, and emerging technologies such as liquid biopsy and AI-assisted prediction models. Results: Global incidence and prevalence continue to rise, driven by population aging and improved detection, while mortality has stabilized or declined in high-income regions. Genomic profiling confirms heterogeneous driver mutations (e.g., KRAS, NRAS, TP53, BRAF), high-risk cytogenetic abnormalities del(17p), t(4;14), and dysregulated pathways (NF-κB, JAK/STAT, PI3K/AKT/mTOR). Diagnostics have advanced through refined IMWG criteria, highly sensitive MRD assays using next-generation flow or sequencing (10⁻⁵-10⁻⁶), and emerging biomarkers such as circulating tumor DNA and serum BCMA. Frontline outcomes have improved with quadruplet regimens combining proteasome inhibitors, immunomodulatory agents, and anti-CD38 antibodies. In relapsed/refractory disease, BCMA-targeted CAR-T cells and bispecific antibodies, including GPRC5D-directed agents, achieve high response rates, though challenges remain in durability, toxicity, and treatment access. Conclusions: Integration of molecular diagnostics, sensitive MRD monitoring, and potent immunotherapies is extending remissions for many patients with MM. Priorities include overcoming resistance, mitigating toxicity, optimizing MRD-guided treatment sequencing, and reducing global disparities in access to advanced therapies. Precision medicine strategies offer a promising pathway to improve survival and quality of life.