World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Review

Volume 000, Number 000, September 2025, pages 000-000

IgM Myeloma: A Comprehensive Overview and Practical Approach to Chemotherapeutic Management

Figure 1. Progression and diagnostic criteria across the monoclonal gammopathy spectrum. Schematic overview of MGUS, smoldering myeloma, and symptomatic multiple myeloma with key thresholds (clonal plasma cells in bone marrow, serum M-protein) and CRAB/end-organ damage criteria [9]. BM: bone marrow; CRAB: hypercalcemia, renal insufficiency, anemia, bone lesions; MGUS: monoclonal gammopathy of uncertain significance.

Figure 2. PRISMA-style study selection for the IgM myeloma review. Database searches of PubMed and Web of Science (English, human studies, last 10 years) identified 1,842 records; 103 full texts were assessed after limits/de-duplication; 49 studies were included in the qualitative synthesis.

Figure 3. Immunophenotype and IGH translocations in IgM myeloma. Common IGH rearrangements at 14q32 (e.g., t(11;14) → CCND1, t(4;14) → FGFR3/NSD2, t(14;16) → MAF; rarer t(6;14) → IRF4/MUM1/CCND3) and representative immunophenotype of IgM myeloma plasma cells: loss of CD19/CD27/CD45 with aberrant CD56/CD20/CD117/cyclin D1. IGH: immunoglobulin heavy chain; WM: Waldenstrom macroglobulinemia.

**Table 1.** Revised IMWG Diagnostic Criteria for MM (Adapted From IMWG Guidelines [9])
CRAB criteria	Any one or more of the following biomarkers of malignancy
The diagnosis requires either clonal plasma cells comprising 10% or more of the bone marrow, or a confirmed biopsy of a bony or extramedullary plasmacytoma, along with at least one of the following defining features of multiple myeloma. CRAB: hypercalcemia, renal insufficiency, anemia, bone lesions; IMWG: International Myeloma Working Group; MM: multiple myeloma; MRI: magnetic resonance imaging; PET-CT: positron emission tomography-computed tomography.
Elevated calcium: Serum calcium level > 0.25 mmol/L (or > 1 mg/dL) above the normal upper limit, or an absolute value exceeding 2.75 mmol/L (11 mg/dL)	Kidney dysfunction: Estimated creatinine clearance < 40 mL/min or serum creatinine > 177 µmol/L (2 mg/dL)	Anemia: Hemoglobin more than 20 g/L below the lower reference limit or total hemoglobin < 100 g/L	Skeletal involvement: One or more osteolytic lesions identified on skeletal survey, CT, or PET-CT	Clonal plasma cells ≥ 60% in bone marrow	Serum free light chain ratio ≥ 100 (involved/uninvolved chains)	More than one focal lesion on MRI studies

Table 1. Revised IMWG Diagnostic Criteria for MM (Adapted From IMWG Guidelines [9])

CRAB criteria

Any one or more of the following biomarkers of malignancy

The diagnosis requires either clonal plasma cells comprising 10% or more of the bone marrow, or a confirmed biopsy of a bony or extramedullary plasmacytoma, along with at least one of the following defining features of multiple myeloma. CRAB: hypercalcemia, renal insufficiency, anemia, bone lesions; IMWG: International Myeloma Working Group; MM: multiple myeloma; MRI: magnetic resonance imaging; PET-CT: positron emission tomography-computed tomography.

Elevated calcium: Serum calcium level > 0.25 mmol/L (or > 1 mg/dL) above the normal upper limit, or an absolute value exceeding 2.75 mmol/L (11 mg/dL)

Kidney dysfunction: Estimated creatinine clearance < 40 mL/min or serum creatinine > 177 µmol/L (2 mg/dL)

Anemia: Hemoglobin more than 20 g/L below the lower reference limit or total hemoglobin < 100 g/L

Skeletal involvement: One or more osteolytic lesions identified on skeletal survey, CT, or PET-CT

Clonal plasma cells ≥ 60% in bone marrow

Serum free light chain ratio ≥ 100 (involved/uninvolved chains)

More than one focal lesion on MRI studies

**Table 2.** Summary of Literature Review Process
Stage	Number of articles
Records identified through database search (PubMed and Web of Science)	1,842
Titles and abstracts screened	103
Studies included in final review	49

Table 2. Summary of Literature Review Process

Stage

Number of articles

Records identified through database search (PubMed and Web of Science)

1,842

Titles and abstracts screened

103

Studies included in final review

**Table 3.** Differential Diagnoses of IgM Myeloma
Differential diagnosis	Monoclonal IgM in serum	Bone marrow findings	Clinical features	MYD88 L265P mutation
Adapted from Castillo et al [18], Schuster et al [19], Owen et al [30], and Treon et al [31]. IgM MGUS: IgM monoclonal gammopathy of undetermined significance; WM: Waldenstrom’s macroglobulinemia.
IgM myeloma	Positive	≥ 10% pure plasmocytic morphology	Lytic bone lesions, hypercalcemia, renal failure, anemia	Absent
WM	Positive	≥ 10% lymphoplasmacytic morphology	Hyperviscosity is more common	Present in > 90% of cases
AL amyloidosis	positive	< 20% plasma cells	Pulmonary symptoms, polyneuropathy, lymphadenopathy	Typically absent
IgM MGUS	< 3 g/dL	< 10%	Asymptomatic	Variable
Other IgM-related disorders	Positive	Typically absent	Cold-induced symptoms (e.g., Raynaud’s, acrocyanosis), neuropathy	Variable

Table 3. Differential Diagnoses of IgM Myeloma

Differential diagnosis

Monoclonal IgM in serum

Bone marrow findings

Clinical features

MYD88 L265P mutation

Adapted from Castillo et al [18], Schuster et al [19], Owen et al [30], and Treon et al [31]. IgM MGUS: IgM monoclonal gammopathy of undetermined significance; WM: Waldenstrom’s macroglobulinemia.

IgM myeloma

Positive

≥ 10% pure plasmocytic morphology

Lytic bone lesions, hypercalcemia, renal failure, anemia

Absent

Positive

≥ 10% lymphoplasmacytic morphology

Hyperviscosity is more common

Present in > 90% of cases

AL amyloidosis

positive

< 20% plasma cells

Pulmonary symptoms, polyneuropathy, lymphadenopathy

Typically absent

IgM MGUS

< 3 g/dL

< 10%

Asymptomatic

Variable

Other IgM-related disorders

Positive

Typically absent

Cold-induced symptoms (e.g., Raynaud’s, acrocyanosis), neuropathy

Variable

**Table 4.** ISS for Multiple Myeloma and Estimated Median Survival
ISS stage	Criteria	R-ISS additional criteria	Estimated median survival (years)
Standard-risk cytogenetics = absence of del(17p), t(4;14), or t(14;16). High-risk cytogenetics = presence of del(17p), t(4;14), and/or t(14;16). Adapted From International Staging System for Multiple Myeloma [39, 44]. β2M: β2 microglobulin; Sβ2M: serum β2 microglobulin; ISS: International Staging System; LDH: lactate dehydrogenase.
I	Sβ2M < 3.5 mg/L; serum albumin ≥ 3.5 g/dL	ISS I + standard-risk cytogenetics + normal LDH	> 8 years
II	Sβ2M < 3.5 mg/L; serum albumin < 3.5 g/dL; or β2M 3.5 to 5.5 mg/L, irrespective of serum albumin	Does not meet I or III.	about 6 years
III	Sβ2M ≥ 5.5mg/L	ISS III + (high-risk cytogenetics OR elevated LDH)	about 3 years

Table 4. ISS for Multiple Myeloma and Estimated Median Survival

ISS stage

Criteria

R-ISS additional criteria

Estimated median survival (years)

Standard-risk cytogenetics = absence of del(17p), t(4;14), or t(14;16). High-risk cytogenetics = presence of del(17p), t(4;14), and/or t(14;16). Adapted From International Staging System for Multiple Myeloma [39, 44]. β2M: β2 microglobulin; Sβ2M: serum β2 microglobulin; ISS: International Staging System; LDH: lactate dehydrogenase.

Sβ2M < 3.5 mg/L; serum albumin ≥ 3.5 g/dL

ISS I + standard-risk cytogenetics + normal LDH

> 8 years

Sβ2M < 3.5 mg/L; serum albumin < 3.5 g/dL; or β2M 3.5 to 5.5 mg/L, irrespective of serum albumin

Does not meet I or III.

about 6 years

III

Sβ2M ≥ 5.5mg/L

ISS III + (high-risk cytogenetics OR elevated LDH)

about 3 years