multiple myeloma

multiple myeloma
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Name	Multiple myeloma
Field	Hematology, Oncology
Symptoms	Bone pain, fatigue, infections, anemia, hypercalcemia, renal failure
Onset	Median age ~65–70 years
Causes	Plasma cell neoplasm
Diagnosis	Serum protein electrophoresis, bone marrow biopsy, imaging
Treatment	Chemotherapy, immunotherapy, stem cell transplant, radiotherapy

multiple myeloma is a malignant neoplasm of plasma cells arising in the bone marrow, characterized by clonal proliferation, monoclonal immunoglobulin production, and end-organ damage. It commonly presents with bone lesions, anemia, renal dysfunction, and recurrent infections and is managed by combinations of cytotoxic chemotherapy, immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and hematopoietic stem cell transplantation. Care involves multidisciplinary teams across institutions such as Mayo Clinic, Memorial Sloan Kettering Cancer Center, Dana–Farber Cancer Institute, Johns Hopkins Hospital and collaborations with cooperative groups like SWOG and EORTC.

Signs and symptoms

Patients typically report progressive bone pain, especially in the spine, ribs, pelvis and long bones, often leading to pathological fractures and spinal cord compression seen in emergency departments such as Royal Marsden Hospital and trauma centers like Massachusetts General Hospital. Constitutional features include fatigue and pallor from anemia, reported across cohorts in registries like SEER Program, and symptoms of hypercalcemia such as polyuria and confusion requiring management at centers like Mayo Clinic Arizona and Cleveland Clinic. Renal impairment leading to acute kidney injury is encountered in nephrology units at Mount Sinai Hospital and Toronto General Hospital, while immunodeficiency predisposes to recurrent bacterial, viral and fungal infections treated at tertiary centers including Guy's Hospital and St Thomas' Hospital.

Pathophysiology

The disease originates from post-germinal center B cells differentiating into malignant plasma cells within the bone marrow microenvironment, a process studied at institutions like Institut Pasteur, Karolinska Institutet, and Fred Hutchinson Cancer Center. Genetic alterations such as translocations involving the immunoglobulin heavy chain locus at 14q32 and cyclin D dysregulation, identified by groups at Cold Spring Harbor Laboratory, Wellcome Sanger Institute, and Broad Institute, drive clonal expansion. Interactions with stromal cells, osteoclast-activating factors, and cytokines such as interleukin-6 elucidated in research from National Institutes of Health and Cancer Research UK promote bone resorption and marrow suppression, mirroring findings reported by investigators at University of Texas MD Anderson Cancer Center and European Molecular Biology Laboratory. Clonal evolution and subclonal heterogeneity resembling patterns described in cancer genomics consortia like TCGA and ICGC underlie treatment resistance.

Diagnosis

Diagnostic evaluation combines laboratory, histopathologic and imaging modalities standardized by guidelines from professional societies including International Myeloma Working Group, American Society of Hematology, and European Hematology Association. Serum protein electrophoresis and immunofixation detect monoclonal paraproteins, free light chain assays are performed in reference laboratories at Quest Diagnostics and LabCorp, and urine studies identify Bence Jones proteinuria; bone marrow biopsy demonstrating clonal plasma cells is interpreted at pathology departments such as Mayo Clinic Laboratories and Johns Hopkins Pathology. Cross-sectional imaging with whole-body low-dose CT, MRI and PET-CT—available at centers like Royal Brompton Hospital and Hospital of the University of Pennsylvania—detect lytic lesions and extramedullary disease. Cytogenetics by fluorescence in situ hybridization and next-generation sequencing from platforms at Illumina and Thermo Fisher Scientific stratify risk and inform treatment selection.

Treatment

Initial therapy frequently uses regimens combining proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide), and corticosteroids; these agents were developed with contributions from pharmaceutical companies such as Johnson & Johnson, Celgene Corporation, and Takeda Pharmaceutical Company. Autologous hematopoietic stem cell transplantation remains standard consolidation for eligible patients at transplant centers including Fred Hutchinson Cancer Center and Mayo Clinic; supportive care involves bisphosphonates like zoledronic acid marketed by Novartis and denosumab developed by Amgen. Relapsed/refractory disease is treated with monoclonal antibodies (e.g., daratumumab by Janssen Global Services), antibody–drug conjugates, and chimeric antigen receptor T-cell therapies pioneered at institutions like National Cancer Institute and University of Pennsylvania Hospital. Radiotherapy is used for localized palliation at oncology departments such as Memorial Sloan Kettering Cancer Center.

Prognosis and epidemiology

Survival has improved significantly with modern therapies, documented in outcome studies from registries like SEER Program and cohort analyses from Mayo Clinic and MD Anderson Cancer Center, but prognosis varies with disease stage, cytogenetic risk groups identified by International Myeloma Working Group, and patient comorbidities managed by general hospitals like Royal Infirmary of Edinburgh. Incidence is higher in older adults and shows disparities across populations studied by the World Health Organization and national cancer institutes including Cancer Research UK; median age at diagnosis is approximately 65–70 years. Mortality trends have declined in regions tracked by Eurostat and national statistical offices, though access to novel agents differs between healthcare systems such as the NHS and the United States Department of Veterans Affairs.

Research and emerging therapies

Ongoing clinical trials coordinated by cooperative groups like SWOG, Alliance for Clinical Trials in Oncology, and industry sponsors including Roche and Bristol Myers Squibb investigate bispecific antibodies, next-generation proteasome inhibitors, selinexor developed through consortia at MD Anderson, and CAR T-cell constructs targeting BCMA refined at University of Pennsylvania and Zhejiang University. Translational studies at centers such as Dana–Farber Cancer Institute, Imperial College London, and Shanghai Jiao Tong University explore microenvironment modulation, vaccine approaches, and minimal residual disease assessment using techniques validated by European Society for Medical Oncology and International Myeloma Working Group. Global initiatives by organizations like ASCO and Multiple Myeloma Research Foundation aim to expand access to novel agents and harmonize biomarker-driven trials.

Category:Blood cancers