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Characteristics and clinical course of younger patients with asymptomatic monoclonal gammopathies

Eirini Solia1, Foteini Theodorakakou1, Panagiotis Malandrakis1

  • 1Department of Clinical Therapeutics, Alexandra General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

British Journal of Haematology
|July 13, 2026
PubMed

Insights

Younger patients with monoclonal gammopathies like MGUS, SMM, and aWM show similar biological traits and low progression rates compared to older adults. Protocolized follow-up suggests early detection is safe and effective.

Area of Science:

  • Hematology
  • Oncology
  • Clinical Research

Background:

  • Monoclonal gammopathies of undetermined significance (MGUS), smouldering multiple myeloma (SMM), and asymptomatic Waldenström's macroglobulinaemia (aWM) are precursor plasma cell disorders.
  • These conditions carry a variable risk of progressing to symptomatic hematologic malignancies.
  • Characterizing these precursor conditions in younger populations is crucial for understanding disease trajectories.

Purpose of the Study:

  • To investigate the clinical characteristics and progression patterns of asymptomatic monoclonal gammopathies in patients under 50 and 40 years of age.
  • To compare the progression rates and risk factors in younger patients versus older cohorts.
  • To evaluate the safety and efficacy of protocolized follow-up in this demographic.

Main Methods:

  • Retrospective analysis of 1237 consecutive patients with monoclonal gammopathies.
  • Subgroup analysis of patients <50 years and <40 years, detailing MGUS, SMM, and aWM prevalence.
  • Assessment of progression using SLiM criteria and bone lesion detection; comparison of SMM progression rates adjusted for baseline risk (20/2/20 criteria).

Main Results:

  • Patients <50 years showed a predominance of MGUS and a female demographic; patients <40 years were 71% female, with equal SMM and MGUS prevalence.
  • Progression in patients <50 years occurred via SLiM criteria or bone lesions, with lower 2, 3, and 5-year SMM progression rates (4%, 6%, 12%) compared to older patients (9%, 13%, 20%) before risk adjustment.
  • No patient <50 years with MGUS or aWM progressed; no SMM patients <40 years at high risk progressed within a 3-year median follow-up.

Conclusions:

  • Younger patients (<50 and <40 years) with asymptomatic monoclonal gammopathies share biological features with older patients.
  • Progression rates in younger SMM patients are generally low and comparable to older patients when adjusted for risk.
  • Protocolized surveillance appears safe for younger individuals with MGUS, aWM, and low-risk SMM, indicating a low risk of complications.
Keywords:
MGUSadultsasymptomatic monoclonal gammopathiesplasma cell disordersprogression ratereal‐world evidence

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