Plasma cell neoplasm is an umbrella mature B-cell neoplasm category defined by clonal expansion of immunoglobulin-secreting plasma cells. It spans precursor monoclonal gammopathy, smoldering multiple myeloma, localized plasmacytoma, multiple myeloma, plasma cell leukemia, and monoclonal immunoglobulin deposition disease. This page models mechanisms shared across the plasma-cell-neoplasm category and does not replace narrower subtype entries such as Multiple Myeloma.
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name: Plasma Cell Neoplasm
creation_date: "2026-05-10T16:47:52Z"
updated_date: "2026-05-10T18:05:08Z"
category: Cancer
categories:
- Hematologic Malignancy
- Plasma Cell Neoplasm
- B-cell Neoplasm
synonyms:
- plasma cell dyscrasia
- plasmacytic neoplasm
- plasma cell tumor
description: >-
Plasma cell neoplasm is an umbrella mature B-cell neoplasm category defined
by clonal expansion of immunoglobulin-secreting plasma cells. It spans
precursor monoclonal gammopathy, smoldering multiple myeloma, localized
plasmacytoma, multiple myeloma, plasma cell leukemia, and monoclonal
immunoglobulin deposition disease. This page models mechanisms shared across
the plasma-cell-neoplasm category and does not replace narrower subtype
entries such as Multiple Myeloma.
disease_term:
preferred_term: plasma cell neoplasm
term:
id: MONDO:0004959
label: plasma cell neoplasm
parents:
- neoplasm of mature B-cells
definitions:
- name: Pathologic definition of plasma cell neoplasm
definition_type: CASE_DEFINITION
description: >-
Plasma cell neoplasms are terminally differentiated B-cell neoplasms
characterized by monoclonal immunoglobulin secretion and stepwise
development from a preneoplastic clonal B-cell or plasma-cell proliferation
such as MGUS.
scope: General category definition spanning precursor and malignant plasma-cell disorders.
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Plasma cell neoplasms including multiple myeloma (MM) and related
terminally differentiated B-cell neoplasms are characterized by secretion
of monoclonal immunoglobulin and stepwise development from a preneoplastic
clonal B and/or plasma cell proliferation called monoclonal gammopathy of
undetermined significance (MGUS).
explanation: >-
This classification review provides the category-level definition used to
anchor the page.
has_subtypes:
- name: Monoclonal Gammopathy of Uncertain Significance
display_name: Monoclonal gammopathy of uncertain significance
classification: precursor_state
description: >-
Asymptomatic precursor plasma cell disorder with monoclonal immunoglobulin
and low clonal burden, lacking myeloma-defining end-organ damage.
subtype_term:
preferred_term: monoclonal gammopathy of uncertain significance
term:
id: MONDO:0004225
label: monoclonal gammopathy of uncertain significance
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Plasma cell neoplasms including multiple myeloma (MM) and related
terminally differentiated B-cell neoplasms are characterized by secretion
of monoclonal immunoglobulin and stepwise development from a preneoplastic
clonal B and/or plasma cell proliferation called monoclonal gammopathy of
undetermined significance (MGUS).
explanation: >-
The review identifies MGUS as the preneoplastic clonal plasma-cell/B-cell
proliferation in the plasma-cell-neoplasm spectrum.
- name: Smoldering Plasma Cell Myeloma
display_name: Smoldering multiple myeloma
classification: precursor_state
description: >-
Asymptomatic intermediate precursor state with clonal plasma-cell or
monoclonal-protein burden above MGUS thresholds but without myeloma-defining
CRAB or SLiM events.
subtype_term:
preferred_term: smoldering plasma cell myeloma
term:
id: MONDO:0005235
label: smoldering plasma cell myeloma
evidence:
- reference: PMID:25439696
reference_title: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
identification of biomarkers associated with near inevitable development
of CRAB features in patients who would otherwise be regarded as having
smouldering multiple myeloma.
explanation: >-
The IMWG consensus distinguishes smoldering multiple myeloma from active
multiple myeloma by the absence of myeloma-defining CRAB features unless
validated biomarkers are present.
- name: Plasma Cell Myeloma
display_name: Multiple myeloma / plasma cell myeloma
classification: clinicopathologic
description: >-
Bone marrow-based plasma cell neoplasm with monoclonal protein and
myeloma-defining manifestations such as osteolytic lesions, anemia, renal
insufficiency, hypercalcemia, or SLiM biomarkers.
subtype_term:
preferred_term: plasma cell myeloma
term:
id: MONDO:0009693
label: plasma cell myeloma
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
The term "multiple myeloma" replaces the term "plasma cell myeloma" used
in the 2016 WHO classification.
explanation: >-
This supports treating multiple myeloma as the current terminology for
the plasma cell myeloma subtype already curated separately in DISMECH.
- name: Plasma Cell Leukemia
classification: clinicopathologic
description: >-
Aggressive plasma cell neoplasm with clonal plasma cells circulating in
peripheral blood.
subtype_term:
preferred_term: plasma cell leukemia
term:
id: MONDO:0018689
label: plasma cell leukemia
evidence:
- reference: PMID:36315921
reference_title: More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia-Like Multiple Myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Primary plasma cell leukemia (PCL) is the most aggressive monoclonal
gammopathy.
explanation: >-
This clinical study supports plasma cell leukemia as the aggressive
circulating-plasma-cell member of the plasma-cell-neoplasm spectrum.
- name: Plasmacytoma
classification: clinicopathologic
description: >-
Localized mass-forming plasma cell neoplasm that may arise in bone or
extraosseous soft tissue and must be distinguished from occult systemic
myeloma.
subtype_term:
preferred_term: plasmacytoma
term:
id: MONDO:0005615
label: plasmacytoma
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
For diagnosis of localized plasma cell tumors, solitary plasmacytoma of
bone, and primary extraosseous plasmacytoma, the importance of excluding
minimal bone marrow infiltration by flow cytometry is emphasized.
explanation: >-
The ICC update identifies localized plasma cell tumors as plasmacytoma
entities and emphasizes marrow flow cytometry to separate them from
systemic disease.
- name: Non-amyloid Monoclonal Immunoglobulin Deposition Disease
display_name: Non-amyloid monoclonal immunoglobulin deposition disease
classification: clinicopathologic
description: >-
Plasma-cell-neoplasm manifestation in which monoclonal immunoglobulin
deposits injure organs, especially kidney, without amyloid fibril
formation.
subtype_term:
preferred_term: non-amyloid monoclonal immunoglobulin deposition disease
term:
id: MONDO:0019463
label: non-amyloid monoclonal immunoglobulin deposition disease
evidence:
- reference: PMID:39196376
reference_title: "Light chain deposition disease: pathogenesis, clinical characteristics and treatment strategies."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Light chain deposition disease (LCDD) is a rare hematologic disorder
characterized by the deposition of non-amyloid monoclonal light chains in
several organs.
explanation: >-
LCDD is a major non-amyloid monoclonal immunoglobulin deposition disease
and supports inclusion of this organ-deposition subtype.
pathophysiology:
- name: Clonal Plasma Cell Expansion
description: >-
A transformed plasma-cell-lineage clone expands in marrow or tissue,
creating the cellular substrate for MGUS, localized plasmacytoma,
systemic myeloma, plasma cell leukemia, or monoclonal immunoglobulin
deposition disease.
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells
in the bone marrow microenvironment, characterized by overproduction of
heavy- and light-chain monoclonal proteins (M-protein).
explanation: >-
This review directly supports clonal plasma-cell proliferation as a core
disease mechanism in the malignant myeloma-spectrum subtype.
cell_types:
- preferred_term: plasma cell
term:
id: CL:0000786
label: plasma cell
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
locations:
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
downstream:
- target: Monoclonal Immunoglobulin Production
description: The expanded plasma-cell clone secretes a monoclonal immunoglobulin or light chain.
- target: Bone Marrow Microenvironment Signaling
description: Marrow interactions support survival and progression of the clonal plasma cells.
- name: Monoclonal Immunoglobulin Production
description: >-
The clonal plasma-cell population produces a monoclonal immunoglobulin or
free light chain that functions as a diagnostic biomarker and can directly
mediate organ injury in deposition diseases or myeloma-related renal
disease.
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Plasma cell neoplasms including multiple myeloma (MM) and related
terminally differentiated B-cell neoplasms are characterized by secretion
of monoclonal immunoglobulin and stepwise development from a preneoplastic
clonal B and/or plasma cell proliferation called monoclonal gammopathy of
undetermined significance (MGUS).
explanation: >-
The abstract explicitly identifies monoclonal immunoglobulin secretion as
a category-defining feature.
cell_types:
- preferred_term: plasma cell
term:
id: CL:0000786
label: plasma cell
biological_processes:
- preferred_term: immunoglobulin production
modifier: ABNORMAL
term:
id: GO:0002377
label: immunoglobulin production
downstream:
- target: Monoclonal Protein-Mediated Organ Injury
description: Monoclonal immunoglobulin or light-chain burden contributes to renal and tissue injury.
- name: Precursor-to-Myeloma Clonal Progression
description: >-
Progression from precursor states toward overt myeloma is shaped by
cumulative genetic lesions and shared signaling programs, including a
MAPK-MYC axis observed across experimental models and patient datasets.
evidence:
- reference: PMID:36928817
reference_title: Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common
MAPK-MYC genetic pathway that accelerated time to progression from
precursor states across genetically heterogeneous MM.
explanation: >-
This model-system and patient-data study links MAPK-MYC signaling to
progression from precursor states across genetically heterogeneous myeloma.
genes:
- preferred_term: MYC
term:
id: hgnc:7553
label: MYC
- preferred_term: KRAS
term:
id: hgnc:6407
label: KRAS
biological_processes:
- preferred_term: MAPK cascade
modifier: INCREASED
term:
id: GO:0000165
label: MAPK cascade
downstream:
- target: Bone Marrow Microenvironment Signaling
description: Progressing clones acquire stronger tumor-supportive and immune-evasive marrow programs.
- name: Immune Evasion and T-Cell Exhaustion
conforms_to: "immune_checkpoint_blockade#Adaptive Immune Resistance"
description: >-
MYC-linked progression remodels marrow T-cell immunity, altering the balance
of CD8-positive T cells and regulatory T cells and producing immune-evasion
states that shape checkpoint and T-cell-redirection responses.
evidence:
- reference: PMID:36928817
reference_title: Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
MYC-dependent time to progression conditioned immune evasion mechanisms
that remodeled the BM microenvironment differently. Rapid MYC-driven
progressors exhibited a high number of activated/exhausted CD8+ T cells
with reduced immunosuppressive regulatory T (Treg) cells, while late MYC
acquisition in slow progressors was associated with lower CD8+ T cell
infiltration and more abundant Treg cells.
explanation: >-
This model-system and patient-data study supports a MYC-linked immune
evasion mechanism involving CD8-positive T cells, regulatory T cells, and
T-cell exhaustion in the marrow microenvironment.
cell_types:
- preferred_term: CD8-positive, alpha-beta T cell
term:
id: CL:0000625
label: CD8-positive, alpha-beta T cell
- preferred_term: regulatory T cell
term:
id: CL:0000815
label: regulatory T cell
biological_processes:
- preferred_term: negative regulation of T cell mediated immunity
modifier: INCREASED
term:
id: GO:0002710
label: negative regulation of T cell mediated immunity
- name: Bone Marrow Microenvironment Signaling
description: >-
Neoplastic plasma cells interact with marrow stromal, immune, and bone-lineage
cells; NF-kappaB and IL6-linked signaling support tumor-cell survival and
progression.
evidence:
- reference: PMID:38714690
reference_title: The genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Moreover, we identify frequent insertional mutagenesis by endogenous
retro-elements as a murine specific mechanism to activate NF-kB and IL6
signaling pathways shared with human MM.
explanation: >-
The Vk*MYC study supports NF-kappaB and IL6 pathway activation as shared
transformation programs between mouse myeloma and human multiple myeloma.
cell_types:
- preferred_term: plasma cell
term:
id: CL:0000786
label: plasma cell
locations:
- preferred_term: bone marrow
term:
id: UBERON:0002371
label: bone marrow
biological_processes:
- preferred_term: canonical NF-kappaB signal transduction
modifier: INCREASED
term:
id: GO:0007249
label: canonical NF-kappaB signal transduction
- preferred_term: response to interleukin-6
modifier: INCREASED
term:
id: GO:0070741
label: response to interleukin-6
downstream:
- target: Clonal Plasma Cell Expansion
description: Survival signaling reinforces persistence and expansion of the malignant plasma-cell clone.
- name: Osteoclast-Osteoblast Uncoupling
description: >-
In myeloma-spectrum plasma cell neoplasm, tumor-marrow interactions increase
osteoclast activation and inhibit osteoblast differentiation, producing
uncoupled bone remodeling and osteolytic disease.
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Interaction of myeloma cells with the bone marrow microenvironment
promotes the release of many biochemical markers including osteoclast
activating factors and osteoblast inhibitory factors.
explanation: >-
The review directly links myeloma-marrow interactions to osteoclast
activation and osteoblast inhibition.
cell_types:
- preferred_term: plasma cell
term:
id: CL:0000786
label: plasma cell
- preferred_term: osteoclast
term:
id: CL:0000092
label: osteoclast
- preferred_term: osteoblast
term:
id: CL:0000062
label: osteoblast
biological_processes:
- preferred_term: osteoclast differentiation
modifier: INCREASED
term:
id: GO:0030316
label: osteoclast differentiation
- preferred_term: bone resorption
modifier: INCREASED
term:
id: GO:0045453
label: bone resorption
downstream:
- target: Osteolysis
description: Uncoupled remodeling produces osteolytic lesions and skeletal-related events.
- name: Monoclonal Protein-Mediated Organ Injury
description: >-
Monoclonal immunoglobulin or free light chains contribute to end-organ
complications, especially renal insufficiency, and are part of the clinical
criteria used to distinguish symptomatic myeloma-spectrum disease from
precursor states.
evidence:
- reference: PMID:25439696
reference_title: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This International Myeloma Working Group consensus updates the disease
definition of multiple myeloma to include validated biomarkers in addition
to existing requirements of attributable CRAB features (hypercalcaemia,
renal failure, anaemia, and bone lesions).
explanation: >-
The IMWG consensus identifies renal failure and related CRAB organ damage
as defining clinical consequences of active myeloma-spectrum disease.
downstream:
- target: Renal Insufficiency
description: Light-chain or monoclonal immunoglobulin burden contributes to renal impairment in symptomatic subtypes.
phenotypes:
- category: Hematologic
name: Monoclonal Gammopathy
diagnostic: true
description: >-
Detection of a monoclonal immunoglobulin or free light chain is a defining
feature across many plasma cell neoplasms, including precursor and
symptomatic states.
phenotype_term:
preferred_term: Paraproteinemia
term:
id: HP:0031047
label: Paraproteinemia
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Plasma cell neoplasms including multiple myeloma (MM) and related
terminally differentiated B-cell neoplasms are characterized by secretion
of monoclonal immunoglobulin and stepwise development from a preneoplastic
clonal B and/or plasma cell proliferation called monoclonal gammopathy of
undetermined significance (MGUS).
explanation: >-
Monoclonal immunoglobulin secretion is explicitly identified as a
category-defining feature.
- category: Hematologic
name: Anemia
description: >-
In marrow-infiltrative plasma cell neoplasms, clonal plasma cells can
suppress normal hematopoiesis and cause anemia, one of the CRAB features of
active myeloma.
phenotype_term:
preferred_term: Anemia
term:
id: HP:0001903
label: Anemia
evidence:
- reference: PMID:25439696
reference_title: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
existing requirements of attributable CRAB features (hypercalcaemia,
renal failure, anaemia, and bone lesions).
explanation: >-
The IMWG diagnostic criteria identify anemia as one of the myeloma-defining
CRAB manifestations.
- category: Skeletal
name: Osteolysis
frequency: VERY_FREQUENT
description: >-
Symptomatic plasma cell myeloma can cause osteolytic lesions through
uncoupled bone remodeling.
phenotype_term:
preferred_term: Osteolysis
term:
id: HP:0002797
label: Osteolysis
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Osteolytic lesions are seen in 80% of patients with MM
explanation: >-
The review provides a direct quantitative statement supporting osteolysis
as very frequent in myeloma-spectrum disease.
- category: Skeletal
name: Bone Pain
description: >-
Osteolytic lesions can cause bone pain and skeletal-related morbidity in
symptomatic myeloma-spectrum plasma cell neoplasm.
phenotype_term:
preferred_term: Bone pain
term:
id: HP:0002653
label: Bone pain
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Osteolytic lesions are seen in 80% of patients with MM which are
complicated frequently by skeletal-related events (SRE) such as
hypercalcemia, bone pain, pathological fractures, vertebral collapse, and
spinal cord compression.
explanation: >-
Bone pain is named as a skeletal-related event complicating osteolytic
disease.
- category: Skeletal
name: Pathologic Fractures
description: >-
Bone weakened by osteolytic disease can fracture, especially in advanced
myeloma-spectrum plasma cell neoplasm.
phenotype_term:
preferred_term: Pathologic fracture
term:
id: HP:0002756
label: Pathologic fracture
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Osteolytic lesions are seen in 80% of patients with MM which are
complicated frequently by skeletal-related events (SRE) such as
hypercalcemia, bone pain, pathological fractures, vertebral collapse, and
spinal cord compression.
explanation: >-
Pathological fractures are listed as skeletal-related events of myeloma
bone disease.
- category: Renal
name: Renal Insufficiency
description: >-
Monoclonal light chains or immunoglobulin deposits can cause renal
impairment in plasma cell neoplasm subtypes.
phenotype_term:
preferred_term: Renal insufficiency
term:
id: HP:0000083
label: Renal insufficiency
evidence:
- reference: PMID:25439696
reference_title: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
existing requirements of attributable CRAB features (hypercalcaemia,
renal failure, anaemia, and bone lesions).
explanation: >-
Renal failure is one of the CRAB features used to define active myeloma.
- category: Metabolic
name: Hypercalcemia
description: >-
Increased bone resorption in myeloma-spectrum disease can raise serum
calcium and contribute to end-organ morbidity.
phenotype_term:
preferred_term: Hypercalcemia
term:
id: HP:0003072
label: Hypercalcemia
evidence:
- reference: PMID:25439696
reference_title: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
existing requirements of attributable CRAB features (hypercalcaemia,
renal failure, anaemia, and bone lesions).
explanation: >-
Hypercalcemia is one of the myeloma-defining CRAB manifestations.
- category: Immunologic
name: Recurrent Infections
description: >-
Suppression of normal immunoglobulin production in symptomatic plasma cell
neoplasm can increase infection susceptibility.
phenotype_term:
preferred_term: Recurrent infections
term:
id: HP:0002719
label: Recurrent infections
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Reduction in normal gammaglobulins (immunoparesis) leads to an increased
risk of infection.
explanation: >-
The review links immunoparesis from myeloma-spectrum disease to increased
infection risk.
biochemical:
- name: Monoclonal immunoglobulin
presence: Positive
notes: >-
Serum or urine monoclonal immunoglobulin, M-protein, or free light chain is
a diagnostic biomarker and a mechanistic contributor to organ damage in
symptomatic subtypes.
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells
in the bone marrow microenvironment, characterized by overproduction of
heavy- and light-chain monoclonal proteins (M-protein).
explanation: >-
The abstract directly identifies monoclonal protein overproduction as a
biochemical feature of myeloma-spectrum disease.
- name: Circulating tumor plasma cells
notes: >-
Circulating tumor plasma cells identify plasma cell leukemia and
ultra-high-risk PCL-like myeloma subsets.
evidence:
- reference: PMID:36315921
reference_title: More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia-Like Multiple Myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our study uncovers that ≥ 2% CTCs is a biomarker of hidden primary PCL and
supports the assessment of CTCs by flow cytometry during the diagnostic
workup of MM.
explanation: >-
Circulating tumor plasma-cell burden is a diagnostic/prognostic biomarker
for PCL-like disease.
genetic:
- name: Cytogenetic Myeloma Subgroups
association: Somatic
notes: >-
Multiple myeloma is now formally subclassified by recurrent cytogenetic
groups including CCND-family translocations, MAF-family translocations, NSD2
translocation, and hyperdiploidy.
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
MM is now formally subdivided into cytogenetic groups, recognizing the
importance of genetics for clinical features and prognosis.
explanation: >-
This classification review supports cytogenetic grouping as a central
genetic axis in the myeloma subtype.
- name: MYC-Driven Progression
association: Somatic
gene_term:
preferred_term: MYC
term:
id: hgnc:7553
label: MYC
notes: >-
MYC activation and MAPK-MYC pathway activity are implicated in progression
from precursor states to overt myeloma.
evidence:
- reference: PMID:38714690
reference_title: The genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans.
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: >-
Multiple myeloma (MM) is a heterogeneous disease characterized by frequent
MYC translocations.
explanation: >-
This mouse-genomics study states that MYC translocations are frequent in
human multiple myeloma and uses a MYC-driven model to study progression.
diagnosis:
- name: Integrated clinicopathologic diagnosis
description: >-
Diagnosis integrates clinical findings, laboratory monoclonal protein
testing, marrow or tissue morphology, and cytogenetic or flow-cytometric
information depending on subtype.
diagnosis_term:
preferred_term: diagnostic procedure
term:
id: MAXO:0000003
label: diagnostic procedure
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Diagnosis of these disorders requires integration of clinical, laboratory,
and morphological features.
explanation: >-
The classification review explicitly states the integrated diagnostic
approach for plasma cell neoplasms.
- name: SLiM-CRAB myeloma-defining criteria
description: >-
Active multiple myeloma is distinguished from precursor states by clonal
plasma-cell burden plus CRAB end-organ damage or validated myeloma-defining
biomarkers.
diagnosis_term:
preferred_term: diagnostic procedure
term:
id: MAXO:0000003
label: diagnostic procedure
evidence:
- reference: PMID:25439696
reference_title: International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This International Myeloma Working Group consensus updates the disease
definition of multiple myeloma to include validated biomarkers in addition
to existing requirements of attributable CRAB features (hypercalcaemia,
renal failure, anaemia, and bone lesions).
explanation: >-
This supports using SLiM biomarkers with CRAB features to define active
myeloma within the plasma-cell-neoplasm spectrum.
- name: Flow cytometry for occult marrow or circulating plasma-cell disease
description: >-
Flow cytometry helps exclude occult marrow involvement in localized
plasmacytoma and identify high-risk circulating tumor plasma-cell burden in
PCL-like myeloma.
diagnosis_term:
preferred_term: diagnostic procedure
term:
id: MAXO:0000003
label: diagnostic procedure
evidence:
- reference: PMID:36414803
reference_title: Plasma cell neoplasms and related entities-evolution in diagnosis and classification.
supports: SUPPORT
evidence_source: OTHER
snippet: >-
For diagnosis of localized plasma cell tumors, solitary plasmacytoma of
bone, and primary extraosseous plasmacytoma, the importance of excluding
minimal bone marrow infiltration by flow cytometry is emphasized.
explanation: >-
The ICC review supports flow cytometry as important in classifying
localized plasma cell tumors.
- reference: PMID:36315921
reference_title: More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia-Like Multiple Myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Our study uncovers that ≥ 2% CTCs is a biomarker of hidden primary PCL and
supports the assessment of CTCs by flow cytometry during the diagnostic
workup of MM.
explanation: >-
This clinical study supports flow-cytometric circulating tumor plasma-cell
assessment during myeloma diagnostic workup.
treatments:
- name: Proteasome Inhibitor, IMiD, and Anti-CD38-Based Systemic Therapy
description: >-
Modern systemic therapy for myeloma-spectrum plasma cell neoplasm commonly
combines proteasome inhibitors, immunomodulatory drugs, corticosteroids, and
anti-CD38 monoclonal antibodies, with regimen selection depending on subtype,
stage, frailty, and transplant eligibility.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: bortezomib
term:
id: CHEBI:52717
label: bortezomib
- preferred_term: lenalidomide
term:
id: CHEBI:63791
label: lenalidomide
- preferred_term: daratumumab
term:
id: NCIT:C74007
label: Daratumumab
evidence:
- reference: PMID:39266530
reference_title: Bispecific antibodies in the treatment of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Upfront use of monoclonal antibodies like daratumumab along with
proteasome inhibitors (PI)s, and immune modulators (IMiD)s have
significantly improved survival and outcomes, but also cause unique
challenges at the time of relapse.
explanation: >-
This treatment review supports the modern systemic backbone of monoclonal
antibodies, proteasome inhibitors, and immunomodulatory drugs.
- name: Bone-Targeted Antiresorptive Therapy
description: >-
Bisphosphonates such as zoledronic acid and the anti-RANKL antibody
denosumab reduce osteoclastic bone resorption and skeletal-related events in
myeloma bone disease.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: zoledronic acid
term:
id: CHEBI:46557
label: zoledronic acid
- preferred_term: denosumab
term:
id: NCIT:C61313
label: Denosumab
target_mechanisms:
- target: Osteoclast-Osteoblast Uncoupling
treatment_effect: INHIBITS
description: >-
Antiresorptive therapy targets osteoclast-driven bone resorption and the
RANKL-mediated uncoupling of marrow bone remodeling.
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
These agents bind to hydroxyapatite and then cause osteoclast apoptosis
by inhibiting mevalonate pathway via inhibition of farnesyl diphosphate
(FPP) synthase
explanation: >-
Bisphosphonate mechanism directly inhibits osteoclast survival and
therefore targets the osteoclast arm of the uncoupling mechanism.
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Denosumab binds to RANKL with high affinity, thereby preventing
activation of RANK and thus inhibiting formation, activation, and
survival of osteoclasts
explanation: >-
Denosumab directly blocks RANKL-dependent osteoclast formation and
survival, matching the modeled osteoclast-osteoblast uncoupling node.
evidence:
- reference: PMID:34201396
reference_title: "Myeloma Bone Disease: A Comprehensive Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Bisphosphonates along with denosumab are the approved modalities of bone
resorptive therapies for management of myeloma bone disease
explanation: >-
The review directly supports bisphosphonate and denosumab bone-targeted
therapy for myeloma-spectrum bone disease.
- name: Autologous Stem Cell Transplantation
description: >-
Upfront autologous stem cell transplantation remains a standard approach for
transplant-eligible symptomatic myeloma-spectrum disease in the novel-drug
era.
treatment_term:
preferred_term: autologous stem cell transplantation
term:
id: MAXO:0010039
label: organ transplantation
evidence:
- reference: PMID:38548963
reference_title: Primary analysis of a prospective cohort study of Japanese patients with plasma cell neoplasms in the novel drug era (2016-2021).
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The 3-year OS rate was 90.3% (95%CI 86.6-93.1%) in the 25% of patients
who received upfront autologous stem cell transplantation (ASCT), versus
just 61.4% (95%CI 58.0-64.6%) in those who did not receive upfront ASCT.
explanation: >-
This prospective plasma-cell-neoplasm cohort supports the continued
clinical importance of upfront ASCT for eligible patients.
- name: CAR T-Cell Therapy
description: >-
Chimeric antigen receptor T-cell therapy redirects immune T cells against
plasma-cell antigens such as BCMA and is used for relapsed multiple myeloma.
treatment_term:
preferred_term: Chimeric Antigen Receptor T-Cell Therapy
term:
id: NCIT:C126102
label: Chimeric Antigen Receptor T-Cell Therapy
evidence:
- reference: PMID:39266530
reference_title: Bispecific antibodies in the treatment of multiple myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Engaging immune T cells for tumour cell kill with chimeric antigenic
T-cell (CAR T-cell) therapy and bispecific antibodies have become important
therapeutic options in relapsed multiple myeloma.
explanation: >-
This review identifies CAR T-cell therapy as an important relapsed-myeloma
treatment option.
- name: Bispecific Antibody Therapy
description: >-
Bispecific antibodies redirect T cells to plasma cell targets such as BCMA
or GPRC5D and are used in heavily pretreated relapsed/refractory multiple
myeloma, with infection, cytopenia, and cytokine release risks.
treatment_term:
preferred_term: pharmacotherapy
term:
id: MAXO:0000058
label: pharmacotherapy
therapeutic_agent:
- preferred_term: bispecific antibody
term:
id: NCIT:C1454
label: Bispecific Antibody
evidence:
- reference: PMID:39001399
reference_title: Bispecific Antibodies for the Management of Relapsed/Refractory Multiple Myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BsAbs against BCMA or GPRC5D have shown impressive clinical activity in
heavily pretreated patients with relapsed/refractory multiple myeloma
(RRMM), with some agents having already received regulatory approval after
the third (by the European Medicines Agency, EMA) or fourth (by the Food
and Drug Administration, FDA) line of therapy;
explanation: >-
This review supports BCMA- or GPRC5D-targeted bispecific antibody therapy
as an approved relapsed/refractory myeloma treatment approach.
- reference: PMID:39001399
reference_title: Bispecific Antibodies for the Management of Relapsed/Refractory Multiple Myeloma.
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The main toxicities include cytokine release syndrome, cytopenias,
hypogammaglobulinemia, and infections;
explanation: >-
This evidence documents the major toxicities that shape clinical use of
bispecific antibodies.
datasets:
Plasma cell neoplasms are terminally differentiated B-cell neoplasms characterized by clonal expansion of plasma cells and typically secretion of a monoclonal immunoglobulin (“M-protein”), with a “stepwise development” from a premalignant clonal stage such as MGUS (fend2023plasmacellneoplasms pages 1-3). A contemporary review states: “Plasma cell neoplasms including multiple myeloma (MM) … are characterized by secretion of monoclonal immunoglobulin and stepwise development from … monoclonal gammopathy of undetermined significance (MGUS).” (Fend et al., 2023, Virchows Archiv; Nov 2023; https://doi.org/10.1007/s00428-022-03431-3) (fend2023plasmacellneoplasms pages 1-3).
Key recent classification concepts in the retrieved sources are from ICC 2022 updates summarized by Fend et al. (2023) (Nov 2023; https://doi.org/10.1007/s00428-022-03431-3): - Terminology: “multiple myeloma” replaces “plasma cell myeloma” (fend2023plasmacellneoplasms pages 1-3). - Cytogenetic subgrouping: MM is subdivided into mutually exclusive cytogenetic groups (eg, CCND family translocations; MAF family translocations; NSD2 translocation; hyperdiploidy), with remaining cases as MM, NOS (fend2023plasmacellneoplasms pages 1-3). - IgM MGUS subdivision: IgM MGUS is subdivided into “IgM MGUS of plasma cell type” (precursor to rare IgM MM; MM-type cytogenetics; no clonal B-cells; MYD88 wild-type) versus IgM MGUS, NOS (fend2023plasmacellneoplasms pages 1-3). - Amyloidosis terminology: systemic “primary AL” renamed immunoglobulin light-chain amyloidosis (AL) and localized AL amyloidosis recognized as distinct (fend2023plasmacellneoplasms pages 1-3). - Plasmacytoma staging nuance: minimal bone marrow infiltration detected by flow cytometry has major prognostic importance for solitary plasmacytoma of bone (fend2023plasmacellneoplasms pages 1-3).
The retrieved corpus did not include authoritative identifier crosswalks (MONDO, ICD-10/11, MeSH, OMIM, Orphanet). Therefore, MONDO ID: not available from retrieved sources.
Most information summarized here comes from aggregated resources including classification reviews and registry/cohort studies (eg, SEER-based incidence trends; national and regional cancer registries; prospective observational cohorts) (mousavi2023apopulationbasedstudy pages 1-2, imounga2023thesingularepidemiology pages 1-2, shibayama2024primaryanalysisof pages 1-2).
PCNs arise through multistep clonal evolution from premalignant stages (MGUS → SMM → MM), with genetics and the bone marrow microenvironment shaping progression (fend2023plasmacellneoplasms pages 1-3, kansal2024towardprecisionmedicine pages 3-6).
A large 2023 study using functional annotation and GWAS meta-analysis (Macauda et al., 2023, Leukemia; Sep 2023; https://doi.org/10.1038/s41375-023-02022-8) reiterates that familial aggregation and the MGUS precursor support heritable susceptibility; it analyzed 5,982 MM cases and 266,173 controls and reports a novel locus (rs28199) with OR 1.18 (95% CI 1.11–1.23) (macauda2023identificationofnovel pages 1-2).
Open Targets (retrieved context) highlights MM-associated/therapeutically relevant targets including CRBN, TNFRSF17 (BCMA), CD38, KRAS/NRAS, FGFR3, and XPO1, reflecting the intersection of genetics and druggability in modern MM management (OpenTargets Search: multiple myeloma).
MGUS prevalence varies geographically (0.24%–9% across studies), affects ~3% of people >50 years in the US, and progresses to MM at ~1% per year (Verma et al., 2023) (verma2023geographicprevalencepatterns pages 1-2).
Protective factors are incompletely defined. A 2023 MGUS review reports diet associations suggesting higher fruit intake may be protective (eg, adolescent fruit intake 3×/week OR 0.62 [95% CI 0.41–0.95]; midlife whole-wheat bread >5/week OR 0.75 [95% CI 0.57–0.99]) (verma2023geographicprevalencepatterns pages 11-13). No specific genetic protective variants were identified in the retrieved corpus.
Direct gene–environment interaction analyses were not available in the retrieved corpus. However, MGUS etiology is hypothesized to involve chronic antigenic stimulation and immune/inflammatory context interacting with clonal genetic lesions (verma2023geographicprevalencepatterns pages 1-2, verma2023geographicprevalencepatterns pages 13-14).
IMWG diagnostic framework incorporates “CRAB” end-organ damage and “SLiM” biomarkers to define myeloma-defining events. A 2024 review summarizes SLiM criteria as: “60% of clonal bone marrow plasma cells, involved/uninvolved serum free light chain ratio ≥100 and >1 focal lesion in MRI studies.” (Morè et al., 2024, Cancers; Jun 2024; https://doi.org/10.3390/cancers16122263) (more2024thechallengingapproach pages 1-2). A separate 2024 review similarly lists SLiM-CRAB components and specifies that presence of any CRAB or SLiM event with ≥10% clonal marrow plasma cells (or a biopsy-proven plasmacytoma) defines active MM (Kansal 2024; Jan 2024; https://doi.org/10.33696/haematology.5.058) (kansal2024towardprecisionmedicine pages 3-6).
SMM is defined as asymptomatic disease meeting M-protein and/or marrow plasma-cell thresholds but without SLiM-CRAB features (fend2023plasmacellneoplasms pages 6-8, kansal2024towardprecisionmedicine pages 3-6).
Because the retrieved corpus did not enumerate phenotype frequencies for classic CRAB components, below are ontology suggestions aligned to the SLiM-CRAB framework: - Bone lesions/osteolysis: HP:0002797 (Osteolysis); HP:0002659 (Skeletal abnormalities) - Hypercalcemia: HP:0003072 - Renal insufficiency: HP:0000083 - Anemia: HP:0001903 - Elevated serum free light chains / monoclonal protein: HP:0030393 (Paraproteinemia; if used) / HP:0030410 (Monoclonal gammopathy; term availability varies) - Bone marrow plasmacytosis: HP:0030180 (Plasmacytosis; if used)
(These HPO suggestions are provided as a mapping aid; the retrieved corpus did not include HPO annotations.)
ICC 2022 emphasizes MM cytogenetic subgrouping (CCND family translocations, MAF family translocations, NSD2 translocation, hyperdiploidy) reflecting clinical/prognostic relevance (fend2023plasmacellneoplasms pages 1-3). Primary cytogenetic features such as trisomies/hyperdiploidy may be present already in MGUS and persist through progression (fend2023plasmacellneoplasms pages 6-8).
Progression is driven by cumulative genetic lesions and dependence on bone marrow microenvironment signals. A 2024 mouse-model review emphasizes that progression from MGUS to MM is “frequently driven by activation of MYC, RAS/mTOR, or NFkB pathways,” and that BCMA signaling via APRIL/BAFF activates NF-κB and supports survival (du2024immunocompetentmousemodels pages 1-3).
The VkMYC immunocompetent mouse model credibly recapitulates diverse, spontaneously acquired genomic alterations. A 2024 Nature Communications study reports that analysis of 119 VkMYC tumors shows recurrent CNVs, structural variants, chromothripsis, driver mutations, APOBEC activity, and decreasing immunoglobulin transcription with increasing proliferation; it identifies murine-specific insertional mutagenesis activating NF-κB and IL6 signaling pathways shared with human MM (Maura et al., 2024; May 2024; https://doi.org/10.1038/s41467-024-48091-w) (maura2024thegenomiclandscape pages 1-2).
Conventional skeletal X-ray is less sensitive; a 2024 review states false-negativity “ranging from 30% to 70%,” and notes whole-body low-dose CT, PET, and whole-body MRI are increasingly central for diagnosis/staging and prognostication (more2024thechallengingapproach pages 1-2).
For localized plasma-cell tumors, ICC 2022 emphasizes that minimal marrow infiltration detected by flow cytometry is of major prognostic importance in solitary plasmacytoma of bone (fend2023plasmacellneoplasms pages 1-3).
Two principal MRD methods are widely used: NGS (immunoglobulin gene clonotype tracking) and high-sensitivity flow cytometry (NGF). - IMWG benchmark: MRD assays should achieve at least 10−5 sensitivity (jevremovic2024reallifesensitivityof pages 1-2). - FDA-approved MRD test: A 2024 letter notes: “Currently the only FDA approved test for MM MRD is NGS-based clonoSEQ© … with the sensitivity of 10−6.” (Jevremovic et al., 2024; Jul 2024; https://doi.org/10.1038/s41408-024-01113-8) (jevremovic2024reallifesensitivityof pages 1-2). A 2023 MRD review similarly notes clonoSEQ as FDA-approved (krzywdzinska2023roleofflow pages 2-3). - Real-world NGF performance: the same 2024 letter reports median collected events ~7–8.3×10^6 yielding practical sensitivities ~2.4–2.8×10−6, approaching NGS-level sensitivity in practice (jevremovic2024reallifesensitivityof pages 1-2). - NGF vs NGS comparison (China cohort): NGS showed LOD ~10−6 and detected MRD in 6/7 pre-ASCT samples vs NGF in 1/7, with 79.1% concordance overall (Zhou et al., 2024; Mar 2024; https://doi.org/10.1007/s12672-024-00938-w) (zhou2024evaluationofnextgeneration pages 1-3). - Deep MRD for treatment decisions: MRD2STOP (2024; https://doi.org/10.1038/s41408-024-01156-x) used PET, BM flow (LoD 10−5) and BM clonoSEQ (LoD 10−6) for eligibility; CD138+ enrichment enabled ~10−7 sensitivity, and clonoSEQ LoD is reported as 6.8×10−7 with LOQ 1.76×10−6 under specified input conditions (derman2024discontinuationofmaintenance pages 1-2).
A SEER-22 population analysis used ICD-O-3 morphological codes 9731 (solitary plasmacytoma of bone), 9732 (plasma cell myeloma), and 9734 (extraosseous plasmacytoma) (Mousavi et al., 2023; Nov 2023; https://doi.org/10.1038/s41598-023-47906-y) (mousavi2023apopulationbasedstudy pages 1-2). Key findings include: - 193,530 plasma cell myeloma cases (2000–2019), with 85.51% age ≥55 and 54.82% male (mousavi2023apopulationbasedstudy pages 1-2). - Age-standardized incidence (all ages) ~7.8 per 100,000 for both sexes (women 7.86; men 7.84), with small positive AAPCs over 2000–2019 (mousavi2023apopulationbasedstudy pages 8-10). - Marked racial disparity: Non-Hispanic Black incidence highest (women 11.65; men 15.64 per 100,000) (mousavi2023apopulationbasedstudy pages 8-10). - Plasmacytomas are rare with low ASIRs (eg, extraosseous plasmacytoma ~0.06 women and ~0.13 men per 100,000 overall) and declining incidence (AAPC negative) (mousavi2023apopulationbasedstudy pages 10-11).
A table containing ASIR/AAPC stratifications is present in the source and was retrieved as images (Tables 4–6) (mousavi2023apopulationbasedstudy media 89dc06ac, mousavi2023apopulationbasedstudy media e0de6d5f, mousavi2023apopulationbasedstudy media a18865ac).
A cancer registry study reports world-standardized incidence 5.9/100,000 man-years and 7.8/100,000 woman-years with female predominance and younger median age at diagnosis than mainland France (Imounga et al., 2023; Dec 2023; https://doi.org/10.3390/cancers16010178) (imounga2023thesingularepidemiology pages 1-2, imounga2023thesingularepidemiology pages 2-4).
A prospective Japanese observational cohort in the “novel drug era” (2016–2021; analysis of 2016–2018 diagnoses) reports a 3-year OS of 70.0% among treated symptomatic PCN (n=1284), with much higher 3-year OS among those receiving upfront autologous stem cell transplant (ASCT) (90.3%) vs those not receiving ASCT (61.4%) (Shibayama et al., 2024; Mar 2024; https://doi.org/10.1007/s12185-024-03754-8) (shibayama2024primaryanalysisof pages 1-2).
Jelinek et al. (2023) report that patients with 2%–20% circulating tumor plasma cells had markedly shorter PFS and OS than those with <2% (example cohort: PFS 3.1 vs 15.6 months; OS 14.6 vs 33.6 months) (https://doi.org/10.1200/JCO.22.01226) (jelinek2023morethan2% pages 1-2).
Modern MM outcomes improved through proteasome inhibitors, IMiDs, and anti-CD38 monoclonal antibodies (daratumumab, isatuximab), with newer immunotherapies (CAR-T and bispecific antibodies) producing deep responses but novel toxicities (CRS, neurotoxicity, infections) (more2024thechallengingapproach pages 1-2).
A 2024 review summarizes: - KarMMa-3: ide-cel ORR 71% vs 42% control; median PFS 13.3 vs 4.4 months (mirvis2024arewethere pages 3-4). - CARTITUDE-1: cilta-cel ORR 97%, 67% sCR; median PFS 34.9 months (mirvis2024arewethere pages 3-4).
Real-world sequential BCMA targeting: a multi-center real-world cohort of commercial ide-cel found lower outcomes in patients previously exposed to BCMA-targeted therapy (ORR 74% vs 88%; median PFS 3.2 vs 9.0 months) (Ferreri et al., 2023; Aug 2023; https://doi.org/10.1038/s41408-023-00886-8) (ferreri2023realworldexperienceof pages 1-2).
A 2024 review reports that these BsAbs achieve ORR exceeding 60% and CR rates ~25–50% with median PFS around 1 year in heavily pretreated RRMM; key toxicities include CRS, cytopenias, hypogammaglobulinemia, and infections (Tacchetti et al., 2024; Jun 2024; https://doi.org/10.3390/cancers16132337) (tacchetti2024bispecificantibodiesfor pages 1-2).
Agent-level examples from the retrieved corpus: - Teclistamab (MajesTEC-1): ORR 63% (updated), ≥CR 45.5%, median PFS 11.3 months, median DoR 21.6 months; hematologic toxicity includes neutropenia 71% (65.5% grade ≥3) (tacchetti2024bispecificantibodiesfor pages 5-6). - Infections and CRS (teclistamab): a 2024 review summarizes teclistamab trial data with CRS ~70–72% (mostly grade 1–2), ICANS ~14.5%, and infections 76.4% (44.8% grade ≥3) (Parrondo et al., 2024; Apr 2024; https://doi.org/10.3389/fonc.2024.1394048) (parrondo2024bispecificantibodiesfor pages 2-3). - Regulatory timeline and indications: elranatamab was FDA-approved Aug 2023 after ≥4 prior lines including PI/IMiD/anti-CD38 (Devasia et al., 2024; Sep 2024; https://doi.org/10.1038/s41408-024-01139-y) (devasia2024bispecificantibodiesin pages 3-4).
Continuous bispecific dosing “until disease progression” raises infection risk, cost, and biologic concerns (T-cell exhaustion). A 2024 perspective argues for strategies such as less-frequent maintenance dosing or fixed-duration therapy after deep remission to improve the toxicity–efficacy balance (van de Donk et al., 2024; Sep 2024; https://doi.org/10.1158/2643-3230.bcd-24-0124) (donk2024tcell–redirectingbispecific pages 1-2).
(MAXO term IDs were not retrievable from the provided corpus.)
No established primary-prevention interventions exist to prevent transformation to MM. Modifiable risk-factor evidence is strongest for obesity and certain environmental exposures (eg, pesticide-related associations in MGUS literature; chlordecone gradients in Martinique) (nedal2024dietinducedobesityreduces pages 1-2, verma2023geographicprevalencepatterns pages 9-11, houpert2024geographicaldisparitiesin pages 1-2).
Population screening for MGUS is controversial and was not directly addressed in the retrieved corpus. However, MGUS prevalence (~3% age>50) and progression risk (~1%/year) support risk-stratified monitoring paradigms (verma2023geographicprevalencepatterns pages 1-2).
Infection prevention is particularly relevant with T-cell redirectors and CAR-T due to infection burden and hypogammaglobulinemia; continuous bispecific dosing is explicitly associated with “high risk of infections” (donk2024tcell–redirectingbispecific pages 1-2), and teclistamab trials report high infection rates including grade ≥3 events (parrondo2024bispecificantibodiesfor pages 2-3).
A 2024 review of immunocompetent mouse models summarizes key systems used for MM biology and therapy development (Du et al., 2024; Apr 2024; https://doi.org/10.1016/j.hoc.2023.12.014): - 5TMM family (5T2/5T33/5TGM1; C57BL/KaLwRij): IgG-secreting, BM-homing, lytic bone lesions; used for homing, dormancy, bone disease and therapeutic studies; strain-dependent constraints (du2024immunocompetentmousemodels pages 3-4). - Pristane-induced Balb/c plasmacytomas: IL-6 dependent; typically harbor MYC translocations (du2024immunocompetentmousemodels pages 3-4). - Vk*MYC (C57BL/6): indolent, progressive, class-switched, somatically hypermutated, BM-restricted monoclonal PC disease traceable by M-spike; long latency enables secondary lesions; many transplantable lines; useful for immunotherapy and evolution studies (du2024immunocompetentmousemodels pages 4-6).
No single model recapitulates all human MM heterogeneity and microenvironment dependence; model choice should match the question (genetic evolution vs immune microenvironment vs bone disease) (du2024immunocompetentmousemodels pages 6-8, du2024immunocompetentmousemodels pages 8-9).
The table below compiles key entity definitions and threshold-based diagnostic/classification updates from ICC 2022/IMWG found in the retrieved corpus.
| Entity | Key defining / classification point | Specific threshold / update | Source | DOI URL |
|---|---|---|---|---|
| IgM MGUS (plasma cell type) | ICC 2022 subdivides IgM MGUS into plasma cell type vs IgM MGUS, NOS | Plasma cell type is precursor to rare IgM MM; characterized by MM-type cytogenetics, absence of clonal B-cells, and absence of MYD88 mutation (fend2023plasmacellneoplasms pages 1-3) | Fend 2023 | https://doi.org/10.1007/s00428-022-03431-3 |
| Smoldering multiple myeloma (SMM) | Asymptomatic clonal plasma-cell disorder without myeloma-defining events | Serum M-protein ≥30 g/L or urinary M-protein ≥500 mg/24 h and/or clonal BM plasma cells 10–60%, without SLiM-CRAB features (fend2023plasmacellneoplasms pages 6-8, kansal2024towardprecisionmedicine pages 3-6) | Fend 2023; Kansal 2024 | https://doi.org/10.1007/s00428-022-03431-3; https://doi.org/10.33696/haematology.5.058 |
| Multiple myeloma (MM) | Active MM defined by clonal plasma-cell burden plus CRAB or biomarker-defined SLiM events | Requires ≥10% clonal BM plasma cells or biopsy-proven plasmacytoma plus CRAB and/or SLiM criteria (kansal2024towardprecisionmedicine pages 3-6, more2024thechallengingapproach pages 1-2) | Kansal 2024; Morè 2024 | https://doi.org/10.33696/haematology.5.058; https://doi.org/10.3390/cancers16122263 |
| Multiple myeloma (MM) — SLiM biomarkers | IMWG 2014 myeloma-defining biomarkers incorporated into current diagnostic framework | S = BM plasma cells ≥60%; Li = involved/uninvolved FLC ratio ≥100; M = >1 focal MRI lesion >5 mm (kansal2024towardprecisionmedicine pages 3-6, more2024thechallengingapproach pages 1-2) | Kansal 2024; Morè 2024 | https://doi.org/10.33696/haematology.5.058; https://doi.org/10.3390/cancers16122263 |
| Multiple myeloma (MM) — ICC 2022 classification | Term “multiple myeloma” replaces “plasma cell myeloma”; formal cytogenetic subgrouping added | Four mutually exclusive cytogenetic groups recognized: CCND family translocations, MAF family translocations, NSD2 translocation, and hyperdiploidy; remainder MM, NOS (fend2023plasmacellneoplasms pages 1-3) | Fend 2023 | https://doi.org/10.1007/s00428-022-03431-3 |
| Solitary plasmacytoma of bone | Diagnosis requires exclusion of systemic marrow disease; ICC emphasizes prognostic value of occult marrow involvement | Minimal BM infiltration detected by flow cytometry is of major prognostic importance (fend2023plasmacellneoplasms pages 1-3) | Fend 2023 | https://doi.org/10.1007/s00428-022-03431-3 |
| Extramedullary / extraosseous plasmacytoma | Localized plasma-cell tumor outside bone marrow; marrow assessment remains important | Minimal BM infiltration by flow cytometry has prognostic importance, though less than for solitary bone plasmacytoma (fend2023plasmacellneoplasms pages 1-3) | Fend 2023 | https://doi.org/10.1007/s00428-022-03431-3 |
| AL amyloidosis | ICC 2022 nomenclature update | “Primary systemic amyloidosis” renamed immunoglobulin light-chain (AL) amyloidosis; localized AL amyloidosis recognized as a distinct entity (fend2023plasmacellneoplasms pages 1-3) | Fend 2023 | https://doi.org/10.1007/s00428-022-03431-3 |
| Plasma cell leukemia (PCL) | Updated IMWG peripheral blood criterion | PCL defined by ≥5% circulating plasma cells in peripheral blood (revised from older 20% threshold) (kansal2024towardprecisionmedicine pages 3-6, jelinek2023morethan2% pages 1-2, kansal2024towardprecisionmedicine pages 8-10) | Kansal 2024; Jelinek 2023 | https://doi.org/10.33696/haematology.5.058; https://doi.org/10.1200/JCO.22.01226 |
| PCL-like multiple myeloma | Flow-cytometry-defined ultra–high-risk MM subset proposed in recent work | >2% circulating tumor plasma cells (CTCs) by flow cytometry identifies PCL-like MM; patients with 2–20% CTCs had markedly inferior outcomes vs <2% (e.g., PFS 3.1 vs 15.6 months; OS 14.6 vs 33.6 months in one cohort) (jelinek2023morethan2% pages 4-5, jelinek2023morethan2% pages 6-7, jelinek2023morethan2% pages 1-2, jelinek2023morethan2% pages 2-3) | Jelinek 2023 | https://doi.org/10.1200/JCO.22.01226 |
Table: This table summarizes the main plasma cell neoplasm entities and the most important ICC 2022/IMWG diagnostic or classification updates, including threshold-based criteria. It is useful as a compact reference for disease knowledge-base curation and clinical concept mapping.
SEER-derived incidence tables for plasma cell myeloma and plasmacytoma subtypes were located in Tables 4–6 of Mousavi et al. (2023) (mousavi2023apopulationbasedstudy media 89dc06ac, mousavi2023apopulationbasedstudy media e0de6d5f, mousavi2023apopulationbasedstudy media a18865ac).
References
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