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smouldering / Asymptomatic myeloma (bsh 2024)


Intro


Definition

  • Smouldering myeloma (SMM) sits between MGUS and Multiple Myeloma (MM)

  • See biochemical criteria below, present without organ or tissue impairment

Epidemiology

  • Est. lifetime prevalence of 1% in UK

  • iStopMM study of >40 yo’s in Iceland = overall prevalence of 0.5% in population.

Screening?

  • Not currently recommended, due to current lack of evidence supporting practicality, cost-effectiveness etc

  • Outcomes from population studies such as iStopMM may change this in the future

diagnostic criteria

Table - IMWG 2014 Diagnostic Criteria. See comments on issues with the SLiM criteria on the Myeloma page

work-up / investigations

When to Ix an asymptomatic monoclonal protein further (ie BM Bx + Imaging)?

  • IgA pp >10g/l

  • IgG pp >15g/l

  • Involved Serum Free light chain >500mg/l

  • Profound unexplained immunoparesis

  • High risk or High-Intermediate risk MGUS (Mayo Clinic 2005, see MGUS page)

Imaging

  • Cross-sectional imaging is mandatory (as opposed to old style plain film skeletal survey)

  • CT skeletal survey / whole body MRI / PET-CT acceptable

Bone Marrow Biopsy

  • Trephine for plasma cell quantification

  • FISH for risk stratification

    • Mandatory panel: t(4;14), t(14;16), t(11;14), del(17p) and gain(1q)

    • Consider also: t(14;20), del(13q) and hyperdiploidy

Consider Amyloidosis

  • As with multiple myeloma, consider possibility of AL amyloidosis during clinical assessment

  • Urine ACR, Troponin and NT-proBNP useful screening tests

  • NB. Cast nephropathy rare with light chains <500mg/l —> consider renal biopsy

Urinary Bence Jones

  • No longer recommended by BSH or NICE for myeloma diagnosis

  • But may have a specific role in risk stratifying some patients with SMM (see guideline for details)

prognosis / risk stratification

General Points

Broadly for all comers, risk of progression from SMM to MM = 10% per year for first 5 years after diagnosis

Falling to 3% per year for the next 5 years and 1% per year after that

This pattern is due to:

  • Random starting time point (due it being an asymptomatic condition)

  • And the underlying biological variability of SMM (from MGUS to high-risk MM)

Mode of progression

  • Blood Cancer Journal 2024 - describes mode of progression in 406 smouldering patients

  • 37% bone lesions, 35% anaemia, 8% hypercalcaemia, 6% renal failure

  • 45% progressions identified on surveillance labs/imaging vs 4% emergency hospital presentations

  • Lots more valuable info in the paper!

Risk Assessment Tools

Many risk scores available and produce discordant results

Imperfect at separating progression from non-progression within 2 years

Nevertheless, BSH recommend using either Mayo 20-20-20 or IMWG model

20-20-20 Mayo 2018 Score

One point for each

  • Plasma cells >20%

  • Paraprotein >20g/l

  • SFLC Ratio >20

Outcomes

  • Low (0) - 10% at 2 years

  • Int (1) - 26% at 2 years

  • High (2+) - 47% at 2 years

IMWG 2020 Score

One point for each

  • Plasma cells >20%

  • Paraprotein >20g/l

  • SFLC Ratio >20

  • High Risk cytogenetics [t(4;14), t(14;16), gain(1q), del(13), del(13q)]

Outcomes

  • Low (0) - 6% at 2 years

  • Low-Int (1) - 23% at 2 years

  • Int (2) - 46% at 2 years

  • High (3+) - 63% at 2 years

monitoring

Many trials, completed and ongoing, investigating early treatment of SMM before progression to MM

—> Currently insufficient evidence to treat SMM (see guideline for detailed review)

Low Risk

  • Monitor 3 monthly for 1 year

  • Then extend to 6-12 monthly indefinitely

  • Move to high risk monitoring if evolving biochemical markers or increasing risk score

Intermediate Risk

  • Monitor 3 monthly for 1-2 years

  • Then extend to 4-6 monthly indefinitely

  • Move to high risk monitoring if evolving biochemical markers or increasing risk score

High Risk

  • Monitor 3 monthly for 5 years

  • Consider clinical trial

  • Consider repeat imaging annually if evolving disease markers

Evolving Biochemical Markers (examples, not exhaustive)

  • Increase in paraprotein at each of first two consecutive follow-ups

  • Increase in paraprotein of >10% in 12 months from baseline >30g/l

  • Increase in paraprotein of >10% in 36 months from baseline <30g/l

  • Decrease in haemoglobin of >5g/l from baseline in 12 months

supportive care

Recommendations:

  • Provide clear patient information, along with psychological support at time of diagnosis & f/up

  • VTE prophylaxis not routinely recommended

  • Offer vaccinations at diagnosis

    • All patients: Pneumococcal, Seasonal Flu, COVID

    • Inactivated Shingles (Shingrix) if >50yo

  • If recurrent or serious infections

    • Check functional pneumococcal antibodies 6 weeks after vaccination

    • Consider prophylactic antibiotics

    • Consider immunoglobulin replacement if low IgG <4g/l plus recurrent or serious infections plus no response to 6 months prophylactic antibiotics plus inadequate response to vaccination

  • Bisphosphonates not routinely recommended