Diagnosis and Management of Multiple Myeloma

Abstract

ultiple myeloma is a hematologic malignancy characterized by abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive osseous bone lesions, acute kidney injury, anemia, and hypercalcemia. The median age at onset of multiple myeloma is 69 years, and approximately 63% of patients diagnosed with multiple myeloma are older than 65 years. 1 In 2021, an estimated 34 290 new diagnoses of multiple myeloma and 12 410 deaths occurred in the US. In 2019, more than 155 688 people were diagnosed with multiple myeloma worldwide. 2 Approximately 100 000 deaths from multiple myeloma occur each year worldwide. 1 This review summarizes current evidence regarding the epidemiology, clinical presentation, diagnosis, and management of multiple myeloma. MethodsA literature search of the PubMed database was performed between January 1, 2000, through October 6, 2021, for Englishlanguage studies of the epidemiology, diagnosis, clinical presentation, and treatment of multiple myeloma. Additional papers were identified from review of the references from identified relevant articles. A total of 111 reports were identified and reviewed. IMPORTANCE Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. Multiple myeloma is diagnosed in an estimated 34 920 people in the US and in approximately 588 161 people worldwide each year. OBSERVATIONS Among patients with multiple myeloma, approximately 73% have anemia, 79% have osteolytic bone disease, and 19% have acute kidney injury at the time of presentation. Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels; serum protein electrophoresis with immunofixation; 24-hour urine protein electrophoresis; and full-body skeletal imaging with computed tomography, positron emission tomography, or magnetic resonance imaging. The Revised International Staging System combines data from the serum biomarkers β 2 microglobulin, albumin, and lactate dehydrogenase in conjunction with malignant plasma cell genomic features found on fluorescence in situ hybridization-t(4;14), del(17p), and t(14;16)-to assess estimated progression-free survival and overall survival. At diagnosis, 28% of patients are classified as having Revised International Staging stage I multiple myeloma, and these patients have a median 5-year survival of 82%. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. This induction therapy combined with autologous hematopoietic stem cell transplantation followed by...

The Role of T Cell Immunity in Monoclonal Gammopathy and Multiple Myeloma: From Immunopathogenesis to Novel Therapeutic Approaches

“…In the late 1990s, the introduction of proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) made a big impact on the therapeutic strategy for MM [3]. Recently, monoclonal antibodies, such as daratumumab, elotuzumab, isatuximab, belantamab mafodotin, as well as histone deacetylating agents, such as panobinostat, selinexor and other investigational agents [4][5][6] have successfully extended the therapeutic options for MM patients [7,8]. In addition, chimeric antigen receptor T cell (CAR-T) therapy is now emerging as a promising approach to treat relapsed/refractory MM (RRMM) [9].…”

“…In addition, chimeric antigen receptor T cell (CAR-T) therapy is now emerging as a promising approach to treat relapsed/refractory MM (RRMM) [9]. Ancillary care for myeloma-related bone disease and other interventions have also resulted in improved survival rates [5,6,10]. However, despite such great therapeutic progress, MM largely remains an incurable disease, with the majority of patients experiencing recurrent relapses, with increasingly shorter periods of remission until death, due to disease-related organ failure and treatment-related complications [1].…”

“…Some patients may show a type of intermediate disease stage between MGUS and MM, termed smoldering multiple myeloma (SMM). By definition, SMM is an asymptomatic malignant condition, characterized by higher levels of M-protein and/or of clonal BM plasma cells compared to MGUS, while sharing with MGUS the absence of end-organ damage and MDEs, and is associated with a 10% annual risk of evolution to overt MM [1,5,6,12,13].…”

Complete Resolution of Skull Base Solitary Plasmacytoma Using Proton-Beam Radiotherapy: A Case Report

“…The diagnostic workup for a solitary plasmacytoma includes a biopsy with evidence of clonal plasma cells, radiographic images demonstrating a lack of systemic lytic lesions, and a bone marrow aspirate and biopsy with no clonal plasma cell presence [ 7 ]. Whole-body computed tomography (CT) or positron emission tomography (PET) imaging are the preferred diagnostic imaging modalities [ 8 ].…”

Identification of an Autophagy-Related Signature Based on Whole Bone Marrow Sequencing for the Prognosis and Immune Microenvironment Characterization of Multiple Myeloma

“…Multiple myeloma (MM) is a clonal proliferative disease of plasma cells whose characteristics include abnormal immunoglobulin production proliferation of malignant plasma cells into the bone marrow, and bone destruction [ 1 ]. Its annual incidence is 4/100,000 people, accounting for approximately 10% of all patients with hematological diseases [ 2 ].…”