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Classifying ultra-high risk smoldering myeloma

Leukemia volume 29, pages 751–753 (2015)Cite this article

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Multiple myeloma (MM) always evolves from a precursor state, either monoclonal gammopathy of undetermined significance or smoldering MM (SMM).1, 2 These precursor states are defined by the absence of MM-related organ damage (‘CRAB’ features: hypercalcemia, renal failure, anemia and bone disease).3 SMM has a highly variable clinical behavior, where some patients have an imminent risk of developing CRAB features and others have a substantially lower risk.4, 5 A recent study has demonstrated that the treatment of high-risk SMM patients with lenalidomide and dexamethasone resulted in fewer CRAB events and improved the overall survival.6 This provocative study suggests that treatment of high-risk SMM may be beneficial. However, identifying patients at ultra-high risk of progression (>80% at 2 years) has proven difficult.7 Both the Mayo Clinic and PETHEMA models fail to define such a high-risk group.4, 5, 8 Furthermore, the PETHEMA model employs a flow cytometry technique, which is not widely available or validated. Genomic approaches have also failed to identify ultra-high risk groups.9, 10, 11 Notably, a recent small study highlighted a fair degree of discordance among these models in SMM.12 Bone marrow plasma cell (BMPC) infiltration of ⩾60% in SMM patients is associated with a 95% risk of developing MM within 2 years.13 A major limitation remains that these models have not been validated in other populations.

Thus, we sought to identify novel biomarkers and validate existing models. We performed a retrospective study of patients with SMM seen at the University of Pennsylvania from 2008–2012. Eligibility was based on ICD-9 codes for MM (203.00–203.02), monoclonal gammopathy (273.1, 357.89) and plasma cell neoplasm (238.6). SMM was diagnosed based on the International Myeloma Working Group (IMWG) criteria3. Progression to active MM was based on clinician judgment that MM-related organ or tissue impairment had occurred or the initiation of MM therapy. The Institutional Review Board of the University of Pennsylvania approved this study.

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Acknowledgements

RM is supported by NIH Cancer Center Support Grant P30-CA016520. AG is supported by NIH T32 training grant CA009615. DV is supported by K23-CA130074 from the National Cancer Institute.

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Authors and Affiliations

  1. Division of Hematology-Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    A J Waxman, A L Garfall, A Cohen, D T Vogl, E A Stadtmauer & B M Weiss

  2. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    R Mick

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  1. A J Waxman
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  2. R Mick
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  3. A L Garfall
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  7. B M Weiss
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Correspondence to B M Weiss.

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Waxman, A., Mick, R., Garfall, A. et al. Classifying ultra-high risk smoldering myeloma. Leukemia 29, 751–753 (2015). https://doi.org/10.1038/leu.2014.313

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