Multiple myeloma classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Shyam Patel [3]

Overview

Multiple myeloma can be classified into several subtypes based on the extent of organ involvement (medullary or extramedullary) and the disease clinical presentation (active symptomatic or smoldering asymptomatic).[1]

Classification

Plasma cell disorders such as multiple myeloma and its related diseases are classified according to disease burden and the extent of organ involvement, as follows:


Disease Diagnostic Criteria Management Approach

Solitary bone plasmacytoma or extraosseous plasmacytoma

  • Biopsy of solid mass with histology and immunohistochemistry consistent with clonal plasma cells as a homogenous infiltrate

plus

  • Absence of clonal plasma cells in bone marrow

plus

  • Absence of end-organ damage such as anemia, hypercalcemia, renal dysfunction, or osseous lesions
  • Localized fractionated radiation therapy of 40-50 Gy over 4 weeks[2]
  • Surgery if there is a need for spine stabilization, fixation of fracture, or decompressive laminectomy[2]
  • Adjuvant chemotherapy is some cases, though not consistently recommended[2]

Monoclonal gammopathy of undetermined significance

  • Presence of M-spike that quantitates < 3 g/dl on protein electrophoresis, or
  • Presence of bone marrow plasma cell burden of < 10%

plus

  • Absence of end-organ damage such as anemia, hypercalcemia, renal dysfunction, or osseous lesions

Monitoring of complete blood count every 6-12 months

Smoldering multiple myeloma

  • Presence of M-spike that quantitates > 3 g/dl on protein electrophoresis, or
  • Presence of bone marrow plasma cell burden of > 10% but < 60%

plus

  • Absence of end-organ damage such as anemia, hypercalcemia, renal dysfunction, or osseous lesions
  • Monitoring of complete blood count at specified intervals, depending on risk stratification
  • Chemotherapy with lenalidomide and dexamethasone for high-risk patients

Active multiple myeloma

  • Presence of M-spike that quantitates > 3 g/dl on protein electrophoresis, or
  • Presence of bone marrow plasma cell burden of > 10% but < 60%

plus

  • Presence of at least one of the following: anemia, hypercalcemia, renal dysfunction, osseous lesions, bone marrow plasma cell burden > 60%, serum free light chain ratio (of involved to uninvolved light chain) > 100, MRI showing > 1 bony lesion of at least 5mm
  • Induction chemotherapy with bortezomib, lenalidomide, and dexamethasone
  • High-dose therapy plus autologous stem cell transplantation
  • Post-transplant lenalidomide maintenance

(Please see Therapy section for details


Multiple myeloma can be classified according to risk status. The risk stratification for multiple myeloma consists of three groups, as follows:[3][4]

Risk group Chromosomal Abnormalities Frequency

Standard risk

  • t(11;14) (CCND1;IgH)
  • t(6;14) (CCND3;IgH)
  • Trisomies (chromosomes 3, 5, 7, 9, 11, 15, 19, 21)
  • Hyperdiploidy

75%

Intermediate Risk

  • t(4;14) (FGFR3;IgH)
  • Gain(1q21)

10%

High risk

  • t(14;16) (IgH;MAF)
  • t(14;20) (IgH;MAFB)
  • del(17p) (p53 deletion)
  • Non-hyperdiploidy

15%|-

References

  1. Alexiou C, Kau RJ, Dietzfelbinger H, Kremer M, Spiess JC, Schratzenstaller B; et al. (1999). "Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts". Cancer. 85 (11): 2305–14. PMID 10357398.
  2. 2.0 2.1 2.2 Caers J, Paiva B, Zamagni E, Leleu X, Bladé J, Kristinsson SY; et al. (2018). "Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated recommendations from a European Expert Panel". J Hematol Oncol. 11 (1): 10. doi:10.1186/s13045-017-0549-1. PMC 5771205. PMID 29338789.
  3. Rajkumar SV (2016). "Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management". Am J Hematol. 91 (7): 719–34. doi:10.1002/ajh.24402. PMC 5291298. PMID 27291302.
  4. Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC; et al. (2016). "Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group". Blood. 127 (24): 2955–62. doi:10.1182/blood-2016-01-631200. PMC 4920674. PMID 27002115.


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