Plasma cell neoplasms are tumors derived from an expansion of mutated mature B-cells and their precursors. These neoplasms include essential monoclonal gammopathy (synonym: monoclonal gammopathy of unknown significance; Chap. 106), smoldering myeloma (Chap. 107), myeloma (Chap. 107), solitary and extramedullary plasmacytomas (Chap. 107), light-chain amyloidosis (Chap. 108), and Waldenström macroglobulinemia (Chap. 109). The prototype of a malignant plasma cell neoplasm is myeloma, which is characterized by complex genetic alterations, best assessed by metaphase cytogenetics, fluorescence in situ hybridization analysis, and gene-expression profiling. The genetic changes are more akin to solid tumors than to hematologic malignancies. Interactions between myeloma cells and the marrow microenvironment affect the survival, proliferation, and drug resistance of myeloma cells, and the development of osteoporosis or osteolysis, which is a hallmark of myeloma. As in most malignancies, a cancer stem cell (e.g., myeloma stem cell) has been identified and is the most likely site of drug resistance, which almost invariably develops during treatment; such cells are not affected by the typical drugs one uses in patients with myeloma. The best prognostic markers in myeloma in order of importance are the presence of (1) specific cytogenetic abnormalities, (2) extent of the disease by appropriate imaging techniques, such as magnetic resonance imaging and/or combined positron emission and computed tomographic imaging, (3) the serum free light-chain level and kappa-to-lambda ratio, and (4) the use of the International Staging System. The development of several classes of drugs over the past decade in combination with transplantation, has improved therapeutic outcomes significantly in patients achieving an unequivocal complete remission. Thus, optimal techniques to assess minimal residual disease have also become important.
Acronyms and Abbreviations
AL, light-chain amyloidosis; BAFF, B-cell activating factor; BCR, B-cell receptor; BMSC, bone mesenchymal stem cell; BTK, Bruton tyrosine kinase; CDR, complementarity determining regions of the heavy chain; CR, complete remission; CSC, cancer stem cell; D, diversity immunoglobulin gene segment; FISH, fluorescence in situ hybridization; FLC, free light chain; GFR, glomerular filtration rate; ICAM-1, intercellular adhesion molecule 1; Ig, immunoglobulin; IGH, immunoglobulin heavy chain; IGF-1, insulin-like growth factor 1; IL, interleukin; IRAK, interleukin-1 receptor-associated kinase; JAK2/STAT3, Janus kinase 2/signal transducers and activators of transcription; JH, joining region immunoglobulin gene segment; M, monoclonal; MBD, myeloma bone disease; MPC, multiparameter flow cytometry; MRD, minimal residual disease; MRI, magnetic resonance imaging; mSMART, Mayo stratification of myeloma and risk-adapted therapy; MYD, myeloid differentiation primary response gene; nCR, near complete remission; NEK2, a serine/threonine kinase; NF-κB, nuclear factor κB; OB, osteoblast; OC, osteoclast; OL, osteolytic lesion; OPG, osteoprotegerin; PCN, plasma cell neoplasm; PDGF, platelet-derived growth factor; PET/CT, 18F-fluorodeoxyglucose positron emission tomography–computed tomography; pP-7, a hyperphosphorylated protein; RAG, recombinase-activating genes; RANK, receptor activator of NF-κB; RARα, retinoic receptor α; RB, retinoblastoma gene sCR, stringent complete remission; sIFE, serum immunofixation electrophoresis; SMM, smoldering myeloma; SP, side population; SPEP, serum protein electrophoresis; ...