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Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load
Open accessAbstract
Purpose: The aim of this study was to analyze chromosomal aberrations in terms of frequency and impact on time to progression in patients with smoldering multiple myeloma (SMM) on the background of clinical prognostic factors. Patients and Methods: The chromosomal abnormalities 1q21, 5p15/5q35, 9q34, 13q14.3, 15q22, 17p13, t(11;14)(q13;q32), and t(4;14)(p16.3;q32) were assessed in CD138-purified myeloma cells by interphase fluorescent in situ hybridization (iFISH) alongside clinical parameters in a consecutive series of 248 patients with SMM. Results: The high-risk aberrations in active myeloma (ie, del(17p13), t(4;14), and +1q21) present in 6.1%, 8.9%, and 29.8% of patients significantly confer adverse prognosis in SMM with hazard ratios (HRs) of 2.90 (95% CI, 1.56 to 5.40), 2.28 (95% CI, 1.33 to 3.91), and 1.66 (95% CI, 1.08 to 2.54), respectively. Contrary to the conditions in active myeloma, hyperdiploidy, present in 43.3% of patients, is an adverse prognostic factor (HR, 1.67; 95% CI, 1.10 to 2.54). Percentage of malignant bone marrow plasma cells assessed by iFISH and combination of M-protein and plasma cell infiltration as surrogates of tumor load significantly confer adverse prognosis with HRs of 4.37 (95% CI, 2.79 to 6.85) and 4.27 (95% CI, 2.77 to 6.56), respectively. In multivariate analysis, high-risk aberrations, hyperdiploidy, and surrogates of tumor load are independently prognostic. Conclusion: The high-risk chromosomal aberrations del(17p13), t(4;14), and +1q21 are adverse prognostic factors in SMM just as they are in active myeloma, independent of tumor mass. Hyperdiploidy is the first example for an adverse prognostic factor in SMM of opposite predictiveness in active myeloma. Risk association of chromosomal aberrations is not only a priori treatment dependent (predictive) but is also an intrinsic property of myeloma cells (prognostic).
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“patients with t(4;14) translocation, del(17p), and gain(1q) are at a higher risk of progression from MGUS or SMM to multiple myeloma.21–23”
From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [22]
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Kyle, R. A., Remstein, E. D., Therneau, T. M., Dispenzieri, A., Kurtin, P. J., Hodnefield, J. M., Larson, D. R., Plevak, M. F., Jelinek, D. F., Fonseca, R., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa070389 · Cited by 921
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International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma
Rajkumar, S. V., Dimopoulos, M. A., Palumbo, A., Blade, J., Merlini, G., Mateos, M.-V., Kumar, S., Hillengass, J., Kastritis, E., Richardson, P., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70442-5 · Cited by 4,978
Self-citationMultiple myeloma: 2020 update on diagnosis, risk‐stratification and management
Rajkumar, S. V. (2020) · American Journal of Hematology · doi:10.1002/ajh.25791 · Cited by 830
Multiple myeloma: 2022 update on diagnosis, risk stratification, and management
Rajkumar, S. V. (2022) · American Journal of Hematology · doi:10.1002/ajh.26590 · Cited by 883
Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management
Rajkumar, S. V. (2024) · American Journal of Hematology · doi:10.1002/ajh.27422 · Cited by 534
Multiple myeloma: 2016 update on diagnosis, risk‐stratification, and management
Rajkumar, S. V. (2016) · American Journal of Hematology · doi:10.1002/ajh.24402 · Cited by 466
Metadata
- Authors
- Neben, K., Jauch, A., Hielscher, T., Hillengass, J., Lehners, N., Seckinger, A., Granzow, M., Raab, M. S., Ho, A. D., Goldschmidt, H., & Hose, D.
- Affiliations
- German Cancer Research Center (DE)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2013-12-01
- Volume
- 31
- Issue
- 34
- Pages
- 4325-4332
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2126894260
- Semantic Scholar
- 3454ef568a1d73e48a414842f0c56b0cc223ddf6
- Cited by
- 233
- References
- 32
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 17 · 2023: 16 · 2022: 13 · 2021: 24 · 2020: 23 · 2019: 13 · 2018: 20 · 2017: 21 · 2016: 18 · 2015: 26 · 2014: 25 · 2013: 2
- FWCI
- 16.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB TRR 79)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- smoldering multiple myeloma, progression to multiple myeloma, chromosomal abnormalities, 17p deletion, hyperdiploidy, tumor burden, prognostic factors, time to progression, M protein, plasma cell infiltration
- MeSH terms
- Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 4, Humans, Multiple Myeloma, Phenotype, Ploidies, Risk Factors, Translocation, Genetic, Multivariate Analysis, Proportional Hazards Models, In Situ Hybridization, Fluorescence, Disease Progression, Genetic Predisposition to Disease, Tumor Burden
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