myelomas

Multiple myeloma is a malignant neoplasm of plasma cells characterized by clonal proliferation in the bone marrow and the production of a monoclonal immunoglobulin or light chains (M-protein). It commonly arises with precursor conditions such as MGUS or smoldering myeloma and can cause bone lesions, anemia, kidney dysfunction, and immune suppression.

Pathophysiology and presentation: The malignant plasma cells accumulate in the marrow, disrupt normal hematopoiesis, and secrete factors that promote bone resorption, leading to lytic lesions and fractures. Patients may experience bone pain, fatigue, infections, hypercalcemia, and swelling. Renal impairment is common due to light chain cast nephropathy and dehydration.

Diagnosis: Suspicion is raised by symptoms and anemia or kidney dysfunction. Evaluation includes serum protein electrophoresis or free light chain assay to detect M-protein, immunofixation, urine protein studies, and a bone marrow biopsy showing clonal plasma cells. Imaging with skeletal surveys, MRI, CT, or PET-CT identifies bone lesions.

Classification and staging: The disease is categorized as symptomatic multiple myeloma or smoldering myeloma; staging uses the International Staging System (ISS) based on beta-2 microglobulin and albumin, with a Revised ISS incorporating LDH and cytogenetic risk. Cytogenetic abnormalities mark prognosis.

Treatment: Management aims to control plasma-cell burden and relieve symptoms. Initial therapy often combines a proteasome inhibitor, an immunomodulatory drug, and dexamethasone; autologous stem cell transplantation is considered for eligible patients. Newer options include monoclonal antibodies such as daratumumab, as well as CAR-T cell therapies and bispecific agents. Maintenance therapy is common after initial response.

Prognosis and epidemiology: Outcomes have improved with novel agents, but prognosis varies by comorbidity and genetic risk; median survival with modern therapy can exceed a decade in some groups. The disease most often affects older adults, with higher incidence in men and people of African descent; incidence is roughly 1–2 per 100,000 per year.