Plasma cell neoplasms (PCNs) are derived from the expansion of mutated, terminally differentiated, postgerminal center B cells. These neoplasms include monoclonal gammopathy of undetermined significance (MGUS) and monoclonal gammopathy of renal significance (MGRS) (Chap. 105), smoldering myeloma (Chap. 106), myeloma (Chap. 106), solitary plasmacytomas and plasmacytomas with minimal marrow involvement (Chap. 106), and light-chain amyloidosis (Chap. 107). The prototypic malignant PCN 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 putative cancer stem cell (eg, 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 used in patients with myeloma. Patients can be prognostically stratified based on the International Staging System (ISS) and revised ISS, which includes cytogenetics and lactate dehydrogenase as well as albumin and β2 microglobulin. The use of combination chemotherapy regimens incorporating drugs targeting myeloma in the context of the marrow microenvironment, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, alone or in combination with transplantation, has significantly improved depth and duration of response, resulting in increased survival. Minimal residual disease negative status is a strong prognostic factor for progression-free and overall survival and is becoming an important endpoint in clinical trials, for new drug registration, and to inform clinical practice.
Acronyms and Abbreviations
AID, activation induced deaminase; AL, light-chain amyloidosis; ALDH, aldehyde dehydrogenase; ASCT, autologous stem cell transplantation; ASO-PCR, allele specific oligonucleotide-polymerase chain reaction; BAFF, B-cell activating factor; BCR, B-cell receptor; BJ, Bence Jones; β2M, β2microglobulin; BMI, body mass index; BMSC, bone marrow stroma stem cell; BTK, Bruton tyrosine kinase; CCL, CC motif ligand; CDR, complementarity determining regions of the heavy chain; CGH, comparative genomic hybridization; CR, complete remission; CRAB, hypercalcemia, renal failure, anemia , lytic bone lesions; CRBN, cereblon; CSR, class switch recombination; CXCL, CXC motif chemokine; CXCR, CXCR chemokine receptor; D, diversity immunoglobulin gene segment; DIKK1, Dickkopf-1; ER, endoploasmic reticulum; FDA, Federal Drug Administration; FDG, fluorodeoxyglucose; FGF, fibroblast growth factor; FISH, fluorescence in situ hybridization; FLC, free light chain; GC, germinal center; GEM, Grupo Espanol de Mieloma; GEP, gene expression profile; HGF, hepatocyte growth factor; HIV, human immunodeficiency virus; HSC, hemopoietic stem cell; ICAM-1, intercellular adhesion molecule 1; IFE, immunofixation electrophoresis; Ig, immunoglobulin; IGH, immunoglobulin heavy chain; IGL, immunoglobulin light chain; IGF-1, insulin-like growth factor 1; IL, interleukin; iMiDs, immunomodulatory drugs; IMWG, international myeloma working group; ISS, international staging system; JAK2/STAT3, Janus kinase 2/signal transducers and activators of transcription3; JH, joining region immunoglobulin gene segment; ...