Multiple myeloma: from the genome to precision medicine

Mieloma múltiple: del genoma a la medicina de precisión

Introduction: multiple myeloma (MM) is a clonal plasma cell proliferative disorder characterized by marked biological and clinical heterogeneity. Genomic instability associated with plasma cell maturation leads to recurrent genetic alterations that play a central role in MM pathogenesis. The aim of this review is to describe the genetic architecture of MM and its impact on prognosis and treatment.

Methods: a literature review was conducted focusing on recent advances in the molecular basis of MM, integrating findings from genomics, epigenetics, immunology, and the bone marrow microenvironment, with emphasis on clinical applicability.

Results: genetic alterations in MM are classified as primary and secondary events, which are responsible for disease initiation and progression and may occur in the presence or absence of hyperdiploidy. Interactions with the bone marrow microenvironment promote tumor progression and immune evasion. Detailed molecular characterization has enabled the development of prognostic scoring systems that identify high-risk patients who may benefit from more intensive therapeutic strategies. In addition, novel therapeutic targets have been identified, leading to the development of T-cell–redirecting therapies, including CAR T-cell therapies and bispecific antibodies, which have demonstrated deep and durable responses. A subset of patients with favorable cytogenetics and sustained responses achieves survival beyond 10 years, supporting the concept of functional cure.

Conclusion: integration of multi-omic data and updated prognostic models will enable further advances toward precision medicine, increasing the proportion of patients with long-term remissions while reducing the toxicity associated with continuous treatment.