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Oncology

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High-risk smoldering multiple myeloma

Overview

Plasma cell disorders constitute a spectrum ranging from premalignant conditions (monoclonal gammopathy of unknown significance [MGUS]) and smoldering multiple myeloma (SMM) to symptomatic malignancy (multiple myeloma [MM])1

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IMWG diagnostic criteria for plasma cell disorders

IMWG diagnostic criteria for plasma cell disorders are based on serum and/or urine M-protein, BMPC, and MM defining events1

m-protien-icon

M-protein1 serum urine

bmpc-Icon

BMPC1

mm-events-icon

MM defining
events1

MGUSa
Incidence2: 60–120
per 100,000

SMM
Incidence2: 0.4-0.9
per 100,000

MM
Incidence3: 7.2
per 100,000

<3 g/dL
<500 mg/24h

<3 g/dL
≥500 mg/24 h

N/A

<10%

10–60%

≥10% or biopsy-proven
plasmacytoma

None

CRAB symptoms or
SLiM biomarkers

  • CRAB criteria: hypercalcemia, renal insufficiency, anemia, bone lesions1

  • SLiM criteria: ≥60% BMPC, Serum FLCr ≥100, >1 focal lesion on MRI1

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MGUS and SMM risk of progression to MM

front-figure

Error bars denote 95% confidence intervals. Figure reproduced with permission

from: Kyle RA, et al. N Engl J Med. 2007;356(25):2582–90.4

Within 10 years of SMM diagnosis, about 70% of patients with SMM will progress to MM5

  • In the first 5 years, patients with SMM progress to MM at a rate of 10% per year5
  • Between 5 to 10 years, the progression rate drops to 3% per year5
  • After 10 years, the risk of progression is 1%, the same rate as patients with MGUS5
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Risk stratification of SMM

SMM is a heterogeneous disease, and consequently, time to progression to MM may vary significantly5

MAYO 2/20/20 (2018)6
Risk factors
  • BMPC >20%
  • M-protein >2 g/dL
  • FLC ratiob >20
Low-risk
  • No risk factors
  • Risk of progression at 2 years: 10%
Intermediate-risk
  • Any 1 risk factor
  • Risk of progression at 2 years: 26%
High-risk
  • ≥2 risk factors
  • Risk of progression at 2 years: 47%
hrsmm-figure
IMWG 20206
Risk assessment scoring toolc
BMPC Score FLC ratiob Score
0–15 0 0-10 0
>15–20 2 10-25 2
>20–30 3 25–40 3
>30–40 5 >40 5
>40 6 >40 5
M-protein Score
0–1.5 0
>1.5-3 3
>3 4
FISH Score
abnormalityd 2
Low-risk
  • Total points: 0–4
  • Risk of progression at 2 years: 4%
Low-intermediate risk
  • Total points: 5–8
  • Risk of progression at 2 years: 26%
Intermediate-risk
  • Total points: 9–12
  • Risk of progression at 2 years: 51%
High-risk
  • Total points: >12
  • Risk of progression at 2 years: 73%
bulb-icon

Risk stratification models continue to evolve as new technological capabilities and risk factors of progression are identified7

Considerations for management of SMM
  • Risk of progression from SMM to MM is variable; therefore, management strategies differ based on the risk of progression4
  • Patients with highest risk could be considered for treatment on clinical trials or per guidelines in addition to observation4
  • See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for MM for more information8