Multiple myeloma: Insights into underlying mechanisms, advances in diagnostic and therapeutic modalities

Multiple myeloma (MM) is characterized by malignant proliferation and accumulation of terminally differentiated antibody-producing plasma cells in bone marrow. The underlying genetic causes of MM are highly complex, involving the loss of function in a myriad of crucial genes, especially those involved in DNA replication fidelity and repair. The important genetic events underscoring MM mutagenesis entail large-scale chromosomal aberrations, localized genetic changes, defective DNA repair mechanisms, point mutation, and mutagenic activity of enzymes such as activation-induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, and catalytic polypeptide (APOBEC). Despite considerable improvement in treatment regimen, MM disease remains incurable for majority of patients with very high mortality. Notably, delay in diagnosis of MM could indirectly contribute to the worse clinical outcomes and lower treatment responsiveness through several mechanisms. Primarily, MM diagnosis relies on histopathological changes and molecular profiling of the patient’s sample. In the past decades, new methods of MM diagnosis and therapeutic approaches have been invented. Together, advances in disease understanding, diagnosis, and novel effective therapeutic interventions have substantially helped slow down and/or arresting the disease progression in the large number of patients, thereby increasing overall survival. This review discusses the genetic causes of MM, clinical presentation, advances in diagnosis, and new therapeutic interventions, including combinations of effective agents targeting relapse/refractory MM.