Diagnostic Impact of SLiM Criteria in Multiple Myeloma: A Real-World Analysis

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In 2014, the diagnostic criteria were revised by the International Myeloma Working Group (IMWG) to enable earlier diagnosis, before irreversible organ damage occurs: SLiM criteria (clonal bone marrow plasma cells ≥60%, serum free light chain ratio ≥100, and >1 focal lesion on magnetic resonance imaging) were added to define criteria for myeloma-defining events (MDE; CRAB+SLiM). The aim of this study was to investigate the diagnostic impact of SLiM criteria in real-world clinical practice and explore their relationship with immunoglobulin subgroups. Methods: A retrospective review of 257 MM patients diagnosed at Seoul National University Hospital between January 2016 and June 2020 was conducted. The number and percentage of patients meeting MDE criteria were evaluated, and the frequency of each criteria was analyzed by immunoglobulin subgroups. Results: Among the 257 patients, 96.9% met CRAB criteria, while 3.1% met only SLiM criteria. 76.7% met SLiM criteria, with subgroups having different proportions of patients meeting each criterion. The light chain (LC) subgroup tended to have the highest number of MDE criteria met. Conclusion: The analysis of MDE criteria revealed that the IMWG criteria revised in 2014 led to a slight increase in MM diagnoses (3.2%), from 249 to 257 patients. The addition of SLiM criteria was slightly more helpful in diagnosing MM than traditional CRAB criteria. In subgroup analysis, the LC subgroup tends to meet more CRAB and SLiM criteria than other subgroups, suggesting an association with advanced stage diseases. An increased serum free light chain ratio may indicate underlying plasma cell proliferative disorders. Multiple myeloma CRAB criteria SLiM criteria Myeloma-defining events criteria Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Multiple myeloma (MM) is the second most common hematologic malignancy, accounting for 10% of hematologic malignancies. As society ages and the incidence of MM is expected to rise, early diagnosis and effective treatment become increasingly important. Historically, hyperCalcemia, Renal insufficiency, Anemia, and osteolytic Bone lesions (CRAB) criteria were regarded as evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorders [1], and have been considered biomarkers to differentiate the precursor conditions of monoclonal gammopathy of undetermined significance and smoldering MM (SMM). However, ultra-high-risk SMM patients who meet only SLiM criteria have a high probability of progression to symptomatic MM within a few years [2,3], highlighting the need for new biomarkers. In 2014, the International Myeloma Working Group (IMWG) diagnostic criteria [4] were revised to require at least one myeloma-defining event (MDE) for a diagnosis of MM. In this revision, the SLiM criteria of clonal bone marrow plasma cells (BMPC) ≥ 60%, serum-free light-chain ratio (SFLCR) ≥ 100 (concentration of the involved free light chain must be ≥ 100 mg/L), and > 1 focal lesion on magnetic resonance imaging ( MRI) were added to the traditional CRAB criteria. To evaluate the diagnostic impact of SLiM criteria in the diagnosis of MM in real-world clinical practice, in this study we aimed to analyze the distribution of patients that met the MDE criteria. Methods We retrospectively reviewed 257 MM patients diagnosed at Seoul National University Hospital between January 2016 and June 2020. This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 2111-148-1276). Clinical, imaging, and laboratory findings at the time of diagnosis were investigated. Immunohistochemical staining with anti-CD138 (Agilent Dako, USA) and immunoglobulin 𝜅/𝜆 antibodies (Sigma-Aldrich, USA) was performed automatically (Ventana Benchmark Ultra, Roche Diagnostics, Switzerland). Serum free light chain (FLC) assay (Freelite, Binding Site Inc., UK) was performed using immunoturbidimetry. From January 2016 to April 2019, the assay was conducted using an Integra 400 analyzer (Roche Diagnostics). From May 2019 to June 2020, the assay was performed using an Optilite analyzer (Binding Site Inc.). The normal FLC 𝜅/𝜆 ratio is 0.26–1.65. Ratios outside this range were defined as monoclonally restricted FLC. BMPC were selected for a high percentage in the differential counts of bone marrow aspiration or biopsy. The International Staging System (ISS) was used to analyze the impact of CRAB and SLiM criteria on MM diagnosis. Statistical analysis was performed using R studio version 3.4.3 (Posit, USA). The Wilcoxon rank-sum test and Chi-square test were used, and p -value < 0.05 considered statistically significant. Results Characteristics of patients The median age of 257 patients was 69 years (interquartile range [IQR], 60–74) and proportion of males was 54.9% (n = 141). Analysis of FLC type distribution showed that 61.5% of the patients (n = 158) had 𝜅, 36.6% (n = 94) had 𝜆, and 1.9% (n = 5) had non-secretory type. The patients were divided into three subgroups: Light chain (LC), 28.0% (n = 72); IgG, 46.7% (n = 120), and non-IgG, 25.3% (n = 65); in the non-IgG subgroup, 23.0% of the total number of patients (n = 59) had IgA, 1.9% (n = 5) had non-secretory, and 0.4% (n = 1) had IgD (Table 1 ). The 𝜆 type was more prevalent in the LC subgroup than in the other subgroups. A higher proportion of the LC subgroup had ISS-III, while a higher proportion of the non-IgG subgroup had ISS-I. Table 1 Laboratory findings in multiple myeloma patients (n = 257) Variable LC subgroup (n = 72) IgG subgroup (n = 120) Non-IgG subgroup (n = 65) Median age, year (IQR) 65.5 (56–74) 69.0 (63–75) 69.0 (60–73) Sex, n (%) Male 39 (54.2%) 60 (50.0%) 42 (64.6%) Female 33 (45.8%) 60 (50.0%) 23 (35.4%) FLC type, n (%) Kappa 40 (55.6%) 79 (65.8%) 39 (60.0%) Lambda 32 (44.4%) 41 (34.2%) 21 (32.3%) Non-secretory 0 (0.0%) 0 (0.0%) 5 (7.7%) ISS stage, n (%) I 27 (37.5%) 46 (38.3%) 30 (46.2%) II 18 (25.0%) 51 (42.5%) 22 (33.8%) III 27 (37.5%) 23 (19.2%) 13 (20.0%) Abbreviations: LC, light chain; IQR, interquartile range; FLC, free light chain; ISS, International staging system Proportions of patients that met MDE criteria Of the 257 patients, 96.9% (n = 249) met at least one CRAB criteria (Table 2 ). The proportions of patients who met each criterion was 68.1% (n = 175) for bone lesions, 63.8% (n = 164) for anemia, 20.6% (n = 53) for renal insufficiency, and 5.8% (n = 15) for hypercalcemia. Bone lesions were detected in 57.7% (138 of 239) of patients by skeletal radiography, in 72.6% (77 of 106) by computed tomography, and in 93.2% (68 of 73) by positron emission tomography/computed tomography. Table 2 Rates of myeloma-defining events (n = 257) Characteristic Value, n (%) CRAB criteria 249 (96.9%) Hypercalcemia (calcium ≥ 110 mg/L) 15 (5.8%) Renal insufficiency (eGFR ≤ 40 mg/dL) 53 (20.6%) Anemia (> 20 g/L below the lowest normal limit) 164 (63.8%) Bone lesions 175 (68.1%) Skeletal radiography 138 of 239 (57.7%) CT 77 of 106 (72.6%) PET-CT 68 of 73 (93.2%) SLiM criteria 197 (76.7%) BMPC ≥ 60% 134 (52.1%) SFLCR ≥ 100 116 (45.1%) > 1 MRI lesions 60 of 121 (49.6%) Abbreviations: CRAB, hyperCalcemia, Renal insufficiency, Anemia, and osteolytic Bone lesions); eGFR, estimated glomerular filtration rate; CT, computed tomography; PEP-CT, positron emission tomography/computed tomography; SLiM, Sixty percent bone marrow plasma cells, Light chain ratio, MRI lesions; BMPC, clonal bone marrow plasma cells; SFLCR, serum free light chain ratio; MRI, magnetic resonance imaging 47.9% (123 of 257) of patients met only one CRAB criterion (Fig. 1 ). The proportion of criteria met was highest for bone lesions (n = 70), followed by anemia (n = 40), and renal insufficiency (n = 10). No patients met only hypercalcemia. As the number of CRAB criteria met increased, the proportion of patients decreased, with only 1.2% (3 of 257) meeting all CRAB criteria. 3.1% (8 of 257) of patients met only SLiM criteria. Among them, all had SFLCR ≥ 100, 75.0% (6 of 8) had BMPC ≥ 60%, and 33.3% (1 of 3) had > 1 MRI lesion. Among the 76.7% (197 of 257) of patients who met at least one SLiM criteria, 52.1% (134 of 257) had BMPC ≥ 60%, 45.1% (116 of 257) had SFLCR ≥ 100, and 49.6% (60 of 121) had > 1 MRI lesion (Table 2 ). 69.3% (178 of 257) had at least one of the BMPC ≥ 60% and SFLCR ≥ 100 criteria, and 28.0% (72 of 257) met both criteria. Most patients met three MDE (CRAB + SLiM) criteria (32.3%, n = 83), followed by two MDE criteria (28.4%, n = 73) (Fig. 2 ). Of the 37 patients who met only one MDE criterion, 51.4% (n = 19) had bone lesions, 29.7% (n = 11) had anemia, 13.5% (n = 5) had renal insufficiency, and 5.4% (n = 2) had SFLCR ≥ 100. None of the patients met only the BMPC ≥ 60%, > 1 MRI lesion, or hypercalcemia criteria. Proportion of MDE criteria by subgroup In the LC subgroup, 30.6% met the renal insufficiency criteria, which was higher than in the other subgroups (IgG, 13.8%; non-IgG, 18.3%) (Fig. 3 ), and 90.9% (20 of 22) of these patients with renal insufficiency met at least one other CRAB criteria (data not shown). The LC subgroup had a higher rate of hypercalcemia but a lower rate of anemia than the other subgroups. In comparison with the other subgroups, the LC subgroup had a higher proportion of patients who met the BMPC ≥ 60% and SFLCR ≥ 100 criteria (68.1% and 72.2%, respectively), and a higher proportion of patients who met at least one (BMPC or SFLCR) criteria (88.9%, 64 of 72); the latter proportion was 60.8% in the IgG group and 63.1% in the non-IgG group ( p < 0.001). The difference between the IgG and non-IgG subgroups was not significant ( p = 0.314). Subgroup analysis of patients who met CRAB criteria (Fig. 4 ) revealed that the LC subgroup (22.2%, 16 of 72) had a significantly higher proportion of patients who met three or more CRAB criteria than the other subgroups (Non-IgG 9.2%, 6 of 65, p -value = 0.039; IgG 5.8%, 7 of 120, p -value < 0.001). Meanwhile, more than half of the IgG subgroup (56.7%, 68 of 120) met only one CRAB criterion. For MDE criteria, the LC subgroup (48.6%, 35 of 72) was also significantly more likely to meet four or more MDE than other subgroups (Non-IgG 16.9%, 11 of 65, p -value < 0.001; IgG 15.0%, 18 of 120, p -value < 0.001) (Fig. 5 ). Discussion This analysis revealed the impact of the IMWG diagnostic criteria revised in 2014 to incorporate the SLiM criteria on the diagnosis of MM in a real-world clinical practice. The added diagnostic criteria allowed more patients with MM to be diagnosed than previously. We also analyzed the proportions of MDE criteria met in subgroups. The proportion of patients who met the CRAB criteria for bone lesions (68.1%) and hypercalcemia (5.8%) was lower than 91.2% and 16.8%, respectively, reported previously by Bao et al. [5]. They also discussed the poor prognosis of patients with hypercalcemia and its association with bone lesions, noting that the proportion of severe hypercalcemia among patients with hypercalcemia at diagnosis was approximately 18%. In our study, none of the patients had severe hypercalcemia, and hypercalcemia occurred only in patients who met all four CRAB criteria. This suggests that the SLiM criteria could be used to diagnose the disease earlier, before hypercalcemia manifests. The proportion of patients who met each SLiM criterion ranged from 45.1–52.1%, which was lower than the proportions of patients with bone lesions (68.1%) and anemia (63.8%). Bone lesions and anemia can occur independently of MM in older adults, which may explain their higher proportions than those of SLiM criteria, which may be more specific to MM. Ho et al. [6] reported that 7.4% of MM patients met only SLiM criteria, which is higher than 3.1% in our study. They didn’t analyze MRI lesions because of underrepresentation. Not all patients underwent whole-body MRI in our study, and regional MRI was often performed in patients with bone lesions. Whole-body MRI can detect small lesions, and 50% of lesions are found outside the axial skeleton, with up to 10% found only in the extremities [7,8]. Patients diagnosed by meeting only one MDE criterion tended to meet the CRAB criteria, which is mostly bone lesions, and none met the > 1 MRI lesion criteria, which may be due to the fact that fewer whole-body MRI were available at the time of diagnosis. It is predicted that performing additional MRI examinations in patients who are asymptomatic but suspected of having MM will result in more patients with MM being diagnosed [9]. These findings imply that in real-world clinical practice, the SLiM criteria do not replace the CRAB criteria, but rather complement them in addition to the existing CRAB criteria. A recent meta-analysis reported that patients who meet only SLiM criteria have a lower rate of progression to MM as diagnosed by using CRAB criteria than previously studies [10], underscoring the importance of using other risk factors and follow-up to assess disease progression, rather than solely relying on the SLiM criteria for diagnosis. In that study, subgroup analysis was not performed, and analysis of the relationship between MDE criteria is needed. The distribution of MDE criteria across different subgroups revealed important differences. The LC subgroup had the highest rates of BMPC ≥ 60% and SFLCR ≥ 100, which are highly specific to MM. A considerable proportion of LC patients (34.8%) met three or more CRAB criteria, highlighting the more aggressive disease state. In previous studies, the LC subgroup was found to be diagnosed at a younger age than the IgG subgroup, but it also showed worse performance status, more bone lesions, renal failure, systemic LC amyloidosis, and lower survival rates, reflecting a later diagnosis in the LC subgroup [11,12]. Similarly, a high SFLCR in the LC subgroup has been reported in many studies [13–16], with tends to be associated with poor survival compared to low SFLCR [17]. In our study, as the number of CRAB criteria met increased, the proportion of the IgG subgroup decreased and the proportion of the LC subgroup increased. Similar trends were also seen when the number of MDE criteria met was four or more compared to three or fewer. The higher the number of CRAB and MDE criteria met, the more advanced ISS stage is and the more likely it is that end organ damage has occurred at multiple sites due to disease progression. In particular, the association between CRAB and SLiM criteria was highest in the LC subgroup, suggesting that the absence of albumin/globulin ratio reverse, which may lead to delayed diagnosis of MM. Limitations First, the exact percentage of BMPC could not be quantified in some patients due to poor BM specimen quality, leading to potential underestimation. Second, not all patients underwent all imaging tests, such as whole-body MRI, which may have failed to detect additional focal lesions. Conclusion The proportion and number of MDE criteria were analyzed to assess their impact on diagnosis at the time MM was diagnosed. We demonstrated that the number of patients diagnosed with MM according to the IMWG diagnostic criteria revised in 2014 increased from 249 to 257 (by 3.2%). Compared to the traditional CRAB criteria, the SLiM criteria were found to be complementary in the diagnosis of MM. In subgroup analysis, the LC subgroup had a lower median age, a more advanced MM stage, and met more CRAB and SLiM criteria, highlighting the importance of subgroup analysis and the need to evaluate SLiM criteria in addition to traditional CRAB criteria when diagnosing MM. An increased SFLCR is a possible indication of underlying disease and should be further evaluated. Declarations Data availability Data supporting the findings are not publicly available due to privacy or ethical restrictions. Data are available upon reasonable request from the corresponding author. Funding This research was supported by grant from the Seoul National University College of Medicine Research Foundation (800-20200319). Financial interests The authors declare no financial interests. Ethics approval and consent to participate This study was performed in line with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 2111-148-1276). Informed consent was waived by our Institutional Review Board because of the retrospective nature of our study. Competing interests The authors declare no competing interests. Author information Authors and Affiliations Department of Laboratory Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea Sooyong Park Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Republic of Korea Sooyong Park, Yoon Hwan Chang Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea Yoon Hwan Chang, Sang Mee Hwang, Hyunwoong Park Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Sang Mee Hwang Department of Laboratory Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea Hyunwoong Park Contributions SYP conducted data collection and analysis, and drafted the manuscript. HWP discussed the results and reviewed the manuscript. YHC and SMH developed the study design, discussed the results and revised the manuscript. The final manuscript was read and met with approval by all authors. Corresponding author Correspondence to Yoon Hwan Chang and Sang Mee Hwang. References Group IMW (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121 (5):749–757. https://doi.org/https://doi.org/10.1046/j.1365-2141.2003.04355.x Dispenzieri A, Stewart AK, Chanan-Khan A, Rajkumar SV, Kyle RA, Fonseca R, Kapoor P, Bergsagel PL, McCurdy A, Gertz MA, Lacy MQ, Lust JA, Russell SJ, Zeldenrust SR, Reeder C, Roy V, Buadi F, Dingli D, Hayman SR, Leung N, Lin Y, Mikhael J, Kumar SK (2013) Smoldering multiple myeloma requiring treatment: time for a new definition? Blood 122 (26):4172–4181. https://doi.org/10.1182/blood-2013-08-520890 Kastritis E, Terpos E, Moulopoulos L, Spyropoulou-Vlachou M, Kanellias N, Eleftherakis-Papaiakovou E, Gkotzamanidou M, Migkou M, Gavriatopoulou M, Roussou M, Tasidou A, Dimopoulos MA (2013) Extensive bone marrow infiltration and abnormal free light chain ratio identifies patients with asymptomatic myeloma at high risk for progression to symptomatic disease. Leukemia 27 (4):947–953. https://doi.org/10.1038/leu.2012.309 Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15 (12):e538-548. https://doi.org/10.1016/s1470-2045(14)70442-5 Bao L, Wang Y, Lu M, Chu B, Shi L, Gao S, Fang L, Xiang Q (2020) Hypercalcemia caused by humoral effects and bone damage indicate poor outcomes in newly diagnosed multiple myeloma patients. Cancer Med 9 (23):8962–8969. https://doi.org/10.1002/cam4.3594 Ho PJ, Moore E, Wellard C, Quach H, Blacklock H, Harrrison SJ, MacDonald EJ, McQuilten ZK, Wood EM, Mollee P, Spencer A (2024) The impact of biomarkers of malignancy (IMWG SLiM criteria) in myeloma in a real-world population: Clinical characteristics, therapy and outcomes from the Australian and New Zealand Myeloma and Related Diseases Registry (ANZ MRDR). Br J Haematol. https://doi.org/10.1111/bjh.19624 Ji M, Wang M, Shih Y-H, Huber J, Fiala MA, Wang R, Sanfilippo KM, Thomas TS, Wang S-Y, Schoen MW, Chang S-H (2024) From criteria to clinic: How updated SLiM CRAB criteria influence multiple myeloma diagnostic activity. Journal of Clinical Oncology 42 (16_suppl):7556–7556. https://doi.org/10.1200/JCO.2024.42.16_suppl.7556 Bäuerle T, Hillengass J, Fechtner K, Zechmann CM, Grenacher L, Moehler TM, Christiane H, Barbara W-G, Neben K, Kauczor H-U, Goldschmidt H, Delorme S (2009) Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance: Importance of Whole-Body versus Spinal MR Imaging. Radiology 252 (2):477–485. https://doi.org/10.1148/radiol.2522081756 Jung S-H, Koh Y, Kim MK, Kim JS, Moon JH, Min C-K, Yoon DH, Yoon S-S, Lee J-J, Hong CM, Kang K-W, Kwon J, Kim KH, Kim DS, Kim SY, Kim S-H, Kim YR, Do YR, Mun Y-C, Park S-S, Park YH, Shin HJ, Eom H-S, Yoon SE, Hwang SM, Lee WS, Lee M-w, Yi JH, Lee JY, Lee JH, Lee HS, Lim S-N, Lim J, Yhim H-Y, Chang YH, Jo J-C, Cho J, Cho H, Choi YS, Cho Hj, Ahn A, Choi JH, Kim HJ, Kim K (2025) Evidence-based Korean guidelines for the clinical management of multiple myeloma: addressing 12 key clinical questions. BR 60 (0). https://doi.org/10.1007/s44313-025-00055-9 Ludwig H, Kainz S, Schreder M, Zojer N, Hinke A (2023) SLiM CRAB criteria revisited: temporal trends in prognosis of patients with smoldering multiple myeloma who meet the definition of 'biomarker-defined early multiple myeloma'-a systematic review with meta-analysis. EClinicalMedicine 58:101910. https://doi.org/10.1016/j.eclinm.2023.101910 Drayson M, Begum G, Basu S, Makkuni S, Dunn J, Barth N, Child JA (2006) Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials. Blood 108 (6):2013–2019. https://doi.org/10.1182/blood-2006-03-008953 Rafae A, Malik MN, Abu Zar M, Durer S, Durer C (2018) An Overview of Light Chain Multiple Myeloma: Clinical Characteristics and Rarities, Management Strategies, and Disease Monitoring. Cureus 10 (8):e3148. https://doi.org/10.7759/cureus.3148 van Rhee F, Bolejack V, Hollmig K, Pineda-Roman M, Anaissie E, Epstein J, Shaughnessy JD, Jr., Zangari M, Tricot G, Mohiuddin A, Alsayed Y, Woods G, Crowley J, Barlogie B (2007) High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood 110 (3):827–832. https://doi.org/10.1182/blood-2007-01-067728 Snozek CL, Katzmann JA, Kyle RA, Dispenzieri A, Larson DR, Therneau TM, Melton LJ, 3rd, Kumar S, Greipp PR, Clark RJ, Rajkumar SV (2008) Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 22 (10):1933–1937. https://doi.org/10.1038/leu.2008.171 García de Veas Silva JL, Bermudo Guitarte C, Menéndez Valladares P, Rojas Noboa JC, Kestler K, Duro Millán R (2016) Prognostic Value of Serum Free Light Chains Measurements in Multiple Myeloma Patients. PLoS One 11 (11):e0166841. https://doi.org/10.1371/journal.pone.0166841 Bal S, Giri S, Godby KN, Costa LJ (2022) Revisiting the impact of immunoglobulin isotypes in multiple myeloma. Annals of Hematology 101 (4):825–829. https://doi.org/10.1007/s00277-022-04783-1 Kyrtsonis M-C, Vassilakopoulos TP, Kafasi N, Sachanas S, Tzenou T, Papadogiannis A, Galanis Z, Kalpadakis C, Dimou M, Kyriakou E, Angelopoulou MK, Dimopoulou MN, Siakantaris MP, Dimitriadou EM, Kokoris SI, Panayiotidis P, Pangalis GA (2007) Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. British Journal of Haematology 137 (3):240–243. https://doi.org/https://doi.org/10.1111/j.1365-2141.2007.06561.x Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6884542","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":472680968,"identity":"8269932e-fe8d-41d0-8aab-f6dfcf54f0c6","order_by":0,"name":"Sooyong Park","email":"","orcid":"","institution":"Chungnam National University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sooyong","middleName":"","lastName":"Park","suffix":""},{"id":472680969,"identity":"889b0ac4-7a60-42c5-9aae-7e3eb5242881","order_by":1,"name":"Yoon Hwan Chang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYFACHoYDHyps5GBcA2K0MB6ccSbNmCQtzId5Ww4nNhCthX9G7oHDvA2H0+fP7jFg+FHDYGzeQECLxI28hINzd6TnbrhzxoCx5xiDmcwBAloMJHIMDrw9Y527Achg4G1gsJEg5DCwFt425nT5GTkGjH+J1XKQt805geFGjgEz0BYzglokzrwxAAWy4YYbaQWHZY5JGBPUwt+eY/wBGJXy8jOSNz58U2NjOIOQFgaBBAT7ANBWghqA1hwgQtEoGAWjYBSMbAAAyGBAn6z5SKMAAAAASUVORK5CYII=","orcid":"","institution":"Seoul National University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yoon","middleName":"Hwan","lastName":"Chang","suffix":""},{"id":472680970,"identity":"5fe073e6-5950-4c4b-853b-b1019e7a8828","order_by":2,"name":"Sang Mee Hwang","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sang","middleName":"Mee","lastName":"Hwang","suffix":""},{"id":472680971,"identity":"90eec2dc-0d40-464e-91fb-82bd1615497a","order_by":3,"name":"Hyunwoong Park","email":"","orcid":"","institution":"Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hyunwoong","middleName":"","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2025-06-13 04:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6884542/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6884542/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85180389,"identity":"855b943f-cd94-4563-843b-06b13e45e34a","added_by":"auto","created_at":"2025-06-23 07:13:44","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":159028,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of patients by the number of CRAB criteria met. Abbreviations: CRAB, hyperCalcemia, Renal insufficiency, Anemia, and osteolytic Bone lesions; MDE, myeloma-defining events; SFLCR, serum free light chain ratio; BMPC, clonal bone marrow plasma cells; MRI, magnetic resonance imaging\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6884542/v1/0988f782f07d3ea9733b1f2c.jpg"},{"id":85180383,"identity":"b182f011-a498-481f-a16e-1ac02a1bc1a9","added_by":"auto","created_at":"2025-06-23 07:13:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":168587,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of patients by the number of MDE criteria met. No patients met all seven MDE criteria. Bone lesions and anemia were more common than BMPC ≥60%, SFLCR ≥100 and other criteria. Abbreviations are the same as in Fig. 1\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6884542/v1/239375f7907ce17d413912ff.jpg"},{"id":85180384,"identity":"a78bdab8-4e43-4d81-84cc-e92ac533c65f","added_by":"auto","created_at":"2025-06-23 07:13:44","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":91232,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of MDE criteria by subgroups. At diagnosis, the LC subgroup was more likely to meet the criteria for hypercalcemia, renal insufficiency, BMPC ≥60%, and SFLCR ≥100 compared to other subgroups, but was less likely to have anemia. Bone lesions were not significantly different among subgroups, and MRI was not performed on all patients, so the exact proportions could not be calculated. Abbreviations: LC, light chain; MDE, myeloma-defining events; BMPC, clonal bone marrow plasma cells; SFLCR, serum free light chain ratio\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6884542/v1/53cbebb3afee69b5ce4b947f.jpg"},{"id":85180390,"identity":"bb4d96e1-1def-4613-86da-65bb17c38846","added_by":"auto","created_at":"2025-06-23 07:13:44","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":111166,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of patients meeting CRAB criteria by subgroup. The LC subgroup had a higher proportion of patients meeting three or more CRAB criteria compared to the other subgroups (non-IgG 9.2%, 6 of 65; IgG 5.8%, 7 of 120). More than half of patients in the IgG subgroup (56.7%, 68 of 120) met only one CRAB criterion. Abbreviations: CRAB, hyperCalcemia, Renal insufficiency, Anemia, and osteolytic Bone lesions; LC, light chain\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6884542/v1/e9909016ebdcc06b1aeb81ff.jpg"},{"id":85181901,"identity":"4d30582c-7fcf-488d-bdb6-5be86afebeb7","added_by":"auto","created_at":"2025-06-23 07:29:44","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":121391,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of patients meeting MDE criteria by subgroup. The LC subgroup was also significantly more likely to meet four or more MDE criteria than other subgroups. Abbreviations: MDE, myeloma-defining events; LC, light chain\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6884542/v1/dc2399f75519b42a2c6e2a9b.jpg"},{"id":85404354,"identity":"bd596eb0-72d9-45bc-b926-aaf49f0c3d15","added_by":"auto","created_at":"2025-06-25 12:47:00","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1347344,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6884542/v1/a97dae7e-9f26-4b28-a52a-987bde2c59fc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic Impact of SLiM Criteria in Multiple Myeloma: A Real-World Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple myeloma (MM) is the second most common hematologic malignancy, accounting for 10% of hematologic malignancies. As society ages and the incidence of MM is expected to rise, early diagnosis and effective treatment become increasingly important. Historically, hyperCalcemia, Renal insufficiency, Anemia, and osteolytic Bone lesions (CRAB) criteria were regarded as evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorders [1], and have been considered biomarkers to differentiate the precursor conditions of monoclonal gammopathy of undetermined significance and smoldering MM (SMM). However, ultra-high-risk SMM patients who meet only SLiM criteria have a high probability of progression to symptomatic MM within a few years [2,3], highlighting the need for new biomarkers. In 2014, the International Myeloma Working Group (IMWG) diagnostic criteria [4] were revised to require at least one myeloma-defining event (MDE) for a diagnosis of MM. In this revision, the SLiM criteria of clonal bone marrow plasma cells (BMPC)\u0026thinsp;\u0026ge;\u0026thinsp;60%, serum-free light-chain ratio (SFLCR)\u0026thinsp;\u0026ge;\u0026thinsp;100 (concentration of the involved free light chain must be \u0026ge;\u0026thinsp;100 mg/L), and \u0026gt;\u0026thinsp;1 focal lesion on magnetic resonance imaging \u003cb\u003e(\u003c/b\u003eMRI) were added to the traditional CRAB criteria. To evaluate the diagnostic impact of SLiM criteria in the diagnosis of MM in real-world clinical practice, in this study we aimed to analyze the distribution of patients that met the MDE criteria.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eWe retrospectively reviewed 257 MM patients diagnosed at Seoul National University Hospital between January 2016 and June 2020. This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 2111-148-1276). Clinical, imaging, and laboratory findings at the time of diagnosis were investigated.\u003c/p\u003e \u003cp\u003eImmunohistochemical staining with anti-CD138 (Agilent Dako, USA) and immunoglobulin \u0026#120581;/\u0026#120582; antibodies (Sigma-Aldrich, USA) was performed automatically (Ventana Benchmark Ultra, Roche Diagnostics, Switzerland).\u003c/p\u003e \u003cp\u003eSerum free light chain (FLC) assay (Freelite, Binding Site Inc., UK) was performed using immunoturbidimetry. From January 2016 to April 2019, the assay was conducted using an Integra 400 analyzer (Roche Diagnostics). From May 2019 to June 2020, the assay was performed using an Optilite analyzer (Binding Site Inc.). The normal FLC \u0026#120581;/\u0026#120582; ratio is 0.26\u0026ndash;1.65. Ratios outside this range were defined as monoclonally restricted FLC. BMPC were selected for a high percentage in the differential counts of bone marrow aspiration or biopsy. The International Staging System (ISS) was used to analyze the impact of CRAB and SLiM criteria on MM diagnosis.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using R studio version 3.4.3 (Posit, USA). The Wilcoxon rank-sum test and Chi-square test were used, and \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of patients\u003c/h2\u003e \u003cp\u003eThe median age of 257 patients was 69 years (interquartile range [IQR], 60\u0026ndash;74) and proportion of males was 54.9% (n\u0026thinsp;=\u0026thinsp;141). Analysis of FLC type distribution showed that 61.5% of the patients (n\u0026thinsp;=\u0026thinsp;158) had \u0026#120581;, 36.6% (n\u0026thinsp;=\u0026thinsp;94) had \u0026#120582;, and 1.9% (n\u0026thinsp;=\u0026thinsp;5) had non-secretory type. The patients were divided into three subgroups: Light chain (LC), 28.0% (n\u0026thinsp;=\u0026thinsp;72); IgG, 46.7% (n\u0026thinsp;=\u0026thinsp;120), and non-IgG, 25.3% (n\u0026thinsp;=\u0026thinsp;65); in the non-IgG subgroup, 23.0% of the total number of patients (n\u0026thinsp;=\u0026thinsp;59) had IgA, 1.9% (n\u0026thinsp;=\u0026thinsp;5) had non-secretory, and 0.4% (n\u0026thinsp;=\u0026thinsp;1) had IgD (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The \u0026#120582; type was more prevalent in the LC subgroup than in the other subgroups. A higher proportion of the LC subgroup had ISS-III, while a higher proportion of the non-IgG subgroup had ISS-I.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory findings in multiple myeloma patients (n\u0026thinsp;=\u0026thinsp;257)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLC subgroup\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;72)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIgG subgroup\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;120)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNon-IgG subgroup\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;65)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian age, year (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65.5 (56\u0026ndash;74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69.0 (63\u0026ndash;75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e69.0 (60\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e42 (64.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33 (45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23 (35.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFLC type, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKappa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40 (55.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e79 (65.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39 (60.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLambda\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41 (34.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-secretory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eISS stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e46 (38.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18 (25.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51 (42.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22 (33.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (19.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: LC, light chain; IQR, interquartile range; FLC, free light chain; ISS, International staging system\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eProportions of patients that met MDE criteria\u003c/h3\u003e\n\u003cp\u003eOf the 257 patients, 96.9% (n\u0026thinsp;=\u0026thinsp;249) met at least one CRAB criteria (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The proportions of patients who met each criterion was 68.1% (n\u0026thinsp;=\u0026thinsp;175) for bone lesions, 63.8% (n\u0026thinsp;=\u0026thinsp;164) for anemia, 20.6% (n\u0026thinsp;=\u0026thinsp;53) for renal insufficiency, and 5.8% (n\u0026thinsp;=\u0026thinsp;15) for hypercalcemia. Bone lesions were detected in 57.7% (138 of 239) of patients by skeletal radiography, in 72.6% (77 of 106) by computed tomography, and in 93.2% (68 of 73) by positron emission tomography/computed tomography.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRates of myeloma-defining events (n\u0026thinsp;=\u0026thinsp;257)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRAB criteria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e249 (96.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypercalcemia (calcium\u0026thinsp;\u0026ge;\u0026thinsp;110 mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (5.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal insufficiency (eGFR\u0026thinsp;\u0026le;\u0026thinsp;40 mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (20.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnemia (\u0026gt;\u0026thinsp;20 g/L below the lowest normal limit)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e164 (63.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e175 (68.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkeletal radiography\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e138 of 239 (57.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 of 106 (72.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePET-CT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 of 73 (93.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSLiM criteria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e197 (76.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMPC\u0026thinsp;\u0026ge;\u0026thinsp;60%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134 (52.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSFLCR\u0026thinsp;\u0026ge;\u0026thinsp;100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116 (45.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;1 MRI lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 of 121 (49.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eAbbreviations: CRAB, hyperCalcemia, Renal insufficiency, Anemia, and osteolytic Bone lesions); eGFR, estimated glomerular filtration rate; CT, computed tomography; PEP-CT, positron emission tomography/computed tomography; SLiM, Sixty percent bone marrow plasma cells, Light chain ratio, MRI lesions; BMPC, clonal bone marrow plasma cells; SFLCR, serum free light chain ratio; MRI, magnetic resonance imaging\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cp\u003e47.9% (123 of 257) of patients met only one CRAB criterion (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The proportion of criteria met was highest for bone lesions (n\u0026thinsp;=\u0026thinsp;70), followed by anemia (n\u0026thinsp;=\u0026thinsp;40), and renal insufficiency (n\u0026thinsp;=\u0026thinsp;10). No patients met only hypercalcemia. As the number of CRAB criteria met increased, the proportion of patients decreased, with only 1.2% (3 of 257) meeting all CRAB criteria.\u003c/p\u003e \u003cp\u003e3.1% (8 of 257) of patients met only SLiM criteria. Among them, all had SFLCR\u0026thinsp;\u0026ge;\u0026thinsp;100, 75.0% (6 of 8) had BMPC\u0026thinsp;\u0026ge;\u0026thinsp;60%, and 33.3% (1 of 3) had\u0026thinsp;\u0026gt;\u0026thinsp;1 MRI lesion.\u003c/p\u003e \u003cp\u003eAmong the 76.7% (197 of 257) of patients who met at least one SLiM criteria, 52.1% (134 of 257) had BMPC\u0026thinsp;\u0026ge;\u0026thinsp;60%, 45.1% (116 of 257) had SFLCR\u0026thinsp;\u0026ge;\u0026thinsp;100, and 49.6% (60 of 121) had\u0026thinsp;\u0026gt;\u0026thinsp;1 MRI lesion (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). 69.3% (178 of 257) had at least one of the BMPC\u0026thinsp;\u0026ge;\u0026thinsp;60% and SFLCR\u0026thinsp;\u0026ge;\u0026thinsp;100 criteria, and 28.0% (72 of 257) met both criteria.\u003c/p\u003e \u003cp\u003eMost patients met three MDE (CRAB\u0026thinsp;+\u0026thinsp;SLiM) criteria (32.3%, n\u0026thinsp;=\u0026thinsp;83), followed by two MDE criteria (28.4%, n\u0026thinsp;=\u0026thinsp;73) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Of the 37 patients who met only one MDE criterion, 51.4% (n\u0026thinsp;=\u0026thinsp;19) had bone lesions, 29.7% (n\u0026thinsp;=\u0026thinsp;11) had anemia, 13.5% (n\u0026thinsp;=\u0026thinsp;5) had renal insufficiency, and 5.4% (n\u0026thinsp;=\u0026thinsp;2) had SFLCR\u0026thinsp;\u0026ge;\u0026thinsp;100. None of the patients met only the BMPC\u0026thinsp;\u0026ge;\u0026thinsp;60%, \u0026gt;\u0026thinsp;1 MRI lesion, or hypercalcemia criteria.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eProportion of MDE criteria by subgroup\u003c/h3\u003e\n\u003cp\u003eIn the LC subgroup, 30.6% met the renal insufficiency criteria, which was higher than in the other subgroups (IgG, 13.8%; non-IgG, 18.3%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), and 90.9% (20 of 22) of these patients with renal insufficiency met at least one other CRAB criteria (data not shown). The LC subgroup had a higher rate of hypercalcemia but a lower rate of anemia than the other subgroups.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn comparison with the other subgroups, the LC subgroup had a higher proportion of patients who met the BMPC\u0026thinsp;\u0026ge;\u0026thinsp;60% and SFLCR\u0026thinsp;\u0026ge;\u0026thinsp;100 criteria (68.1% and 72.2%, respectively), and a higher proportion of patients who met at least one (BMPC or SFLCR) criteria (88.9%, 64 of 72); the latter proportion was 60.8% in the IgG group and 63.1% in the non-IgG group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The difference between the IgG and non-IgG subgroups was not significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.314).\u003c/p\u003e \u003cp\u003eSubgroup analysis of patients who met CRAB criteria (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) revealed that the LC subgroup (22.2%, 16 of 72) had a significantly higher proportion of patients who met three or more CRAB criteria than the other subgroups (Non-IgG 9.2%, 6 of 65, \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;=\u0026thinsp;0.039; IgG 5.8%, 7 of 120, \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Meanwhile, more than half of the IgG subgroup (56.7%, 68 of 120) met only one CRAB criterion. For MDE criteria, the LC subgroup (48.6%, 35 of 72) was also significantly more likely to meet four or more MDE than other subgroups (Non-IgG 16.9%, 11 of 65, \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001; IgG 15.0%, 18 of 120, \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis analysis revealed the impact of the IMWG diagnostic criteria revised in 2014 to incorporate the SLiM criteria on the diagnosis of MM in a real-world clinical practice. The added diagnostic criteria allowed more patients with MM to be diagnosed than previously. We also analyzed the proportions of MDE criteria met in subgroups.\u003c/p\u003e \u003cp\u003eThe proportion of patients who met the CRAB criteria for bone lesions (68.1%) and hypercalcemia (5.8%) was lower than 91.2% and 16.8%, respectively, reported previously by Bao et al. [5]. They also discussed the poor prognosis of patients with hypercalcemia and its association with bone lesions, noting that the proportion of severe hypercalcemia among patients with hypercalcemia at diagnosis was approximately 18%. In our study, none of the patients had severe hypercalcemia, and hypercalcemia occurred only in patients who met all four CRAB criteria. This suggests that the SLiM criteria could be used to diagnose the disease earlier, before hypercalcemia manifests.\u003c/p\u003e \u003cp\u003eThe proportion of patients who met each SLiM criterion ranged from 45.1–52.1%, which was lower than the proportions of patients with bone lesions (68.1%) and anemia (63.8%). Bone lesions and anemia can occur independently of MM in older adults, which may explain their higher proportions than those of SLiM criteria, which may be more specific to MM.\u003c/p\u003e \u003cp\u003eHo et al. [6] reported that 7.4% of MM patients met only SLiM criteria, which is higher than 3.1% in our study. They didn’t analyze MRI lesions because of underrepresentation. Not all patients underwent whole-body MRI in our study, and regional MRI was often performed in patients with bone lesions. Whole-body MRI can detect small lesions, and 50% of lesions are found outside the axial skeleton, with up to 10% found only in the extremities [7,8].\u003c/p\u003e \u003cp\u003ePatients diagnosed by meeting only one MDE criterion tended to meet the CRAB criteria, which is mostly bone lesions, and none met the \u0026gt; 1 MRI lesion criteria, which may be due to the fact that fewer whole-body MRI were available at the time of diagnosis. It is predicted that performing additional MRI examinations in patients who are asymptomatic but suspected of having MM will result in more patients with MM being diagnosed [9].\u003c/p\u003e \u003cp\u003eThese findings imply that in real-world clinical practice, the SLiM criteria do not replace the CRAB criteria, but rather complement them in addition to the existing CRAB criteria. A recent meta-analysis reported that patients who meet only SLiM criteria have a lower rate of progression to MM as diagnosed by using CRAB criteria than previously studies [10], underscoring the importance of using other risk factors and follow-up to assess disease progression, rather than solely relying on the SLiM criteria for diagnosis. In that study, subgroup analysis was not performed, and analysis of the relationship between MDE criteria is needed. The distribution of MDE criteria across different subgroups revealed important differences. The LC subgroup had the highest rates of BMPC ≥ 60% and SFLCR ≥ 100, which are highly specific to MM. A considerable proportion of LC patients (34.8%) met three or more CRAB criteria, highlighting the more aggressive disease state. In previous studies, the LC subgroup was found to be diagnosed at a younger age than the IgG subgroup, but it also showed worse performance status, more bone lesions, renal failure, systemic LC amyloidosis, and lower survival rates, reflecting a later diagnosis in the LC subgroup [11,12]. Similarly, a high SFLCR in the LC subgroup has been reported in many studies [13–16], with tends to be associated with poor survival compared to low SFLCR [17].\u003c/p\u003e \u003cp\u003eIn our study, as the number of CRAB criteria met increased, the proportion of the IgG subgroup decreased and the proportion of the LC subgroup increased. Similar trends were also seen when the number of MDE criteria met was four or more compared to three or fewer.\u003c/p\u003e \u003cp\u003eThe higher the number of CRAB and MDE criteria met, the more advanced ISS stage is and the more likely it is that end organ damage has occurred at multiple sites due to disease progression. In particular, the association between CRAB and SLiM criteria was highest in the LC subgroup, suggesting that the absence of albumin/globulin ratio reverse, which may lead to delayed diagnosis of MM.\u003c/p\u003e "},{"header":"Limitations","content":"\u003cp\u003eFirst, the exact percentage of BMPC could not be quantified in some patients due to poor BM specimen quality, leading to potential underestimation. Second, not all patients underwent all imaging tests, such as whole-body MRI, which may have failed to detect additional focal lesions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe proportion and number of MDE criteria were analyzed to assess their impact on diagnosis at the time MM was diagnosed. We demonstrated that the number of patients diagnosed with MM according to the IMWG diagnostic criteria revised in 2014 increased from 249 to 257 (by 3.2%). Compared to the traditional CRAB criteria, the SLiM criteria were found to be complementary in the diagnosis of MM.\u003c/p\u003e \u003cp\u003eIn subgroup analysis, the LC subgroup had a lower median age, a more advanced MM stage, and met more CRAB and SLiM criteria, highlighting the importance of subgroup analysis and the need to evaluate SLiM criteria in addition to traditional CRAB criteria when diagnosing MM. An increased SFLCR is a possible indication of underlying disease and should be further evaluated.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData supporting the findings are not publicly available due to privacy or ethical restrictions. Data are available upon reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research was supported by grant from the Seoul National University College of Medicine Research Foundation (800-20200319).\u003c/p\u003e\n\u003cp\u003eFinancial interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no financial interests.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 2111-148-1276). Informed consent was waived by our Institutional Review Board because of the retrospective nature of our study.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors and Affiliations\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Laboratory Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSooyong Park\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Laboratory Medicine, Seoul National University Hospital, Seoul, Republic of Korea\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSooyong Park, Yoon Hwan Chang\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYoon Hwan Chang, Sang Mee Hwang, Hyunwoong Park\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSang Mee Hwang\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDepartment of Laboratory Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Republic of Korea\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHyunwoong Park\u003c/p\u003e\n\u003cp\u003eContributions\u003c/p\u003e\n\u003cp\u003eSYP conducted data collection and analysis, and drafted the manuscript. HWP discussed the results and reviewed the manuscript. YHC and SMH developed the study design, discussed the results and revised the manuscript. The final manuscript was read and met with approval by all authors.\u003c/p\u003e\n\u003cp\u003eCorresponding author\u003c/p\u003e\n\u003cp\u003eCorrespondence to Yoon Hwan Chang and Sang Mee Hwang.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003e Group IMW (2003) Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 121 (5):749\u0026ndash;757. https://doi.org/https://doi.org/10.1046/j.1365-2141.2003.04355.x\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Dispenzieri A, Stewart AK, Chanan-Khan A, Rajkumar SV, Kyle RA, Fonseca R, Kapoor P, Bergsagel PL, McCurdy A, Gertz MA, Lacy MQ, Lust JA, Russell SJ, Zeldenrust SR, Reeder C, Roy V, Buadi F, Dingli D, Hayman SR, Leung N, Lin Y, Mikhael J, Kumar SK (2013) Smoldering multiple myeloma requiring treatment: time for a new definition? Blood 122 (26):4172\u0026ndash;4181. https://doi.org/10.1182/blood-2013-08-520890\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Kastritis E, Terpos E, Moulopoulos L, Spyropoulou-Vlachou M, Kanellias N, Eleftherakis-Papaiakovou E, Gkotzamanidou M, Migkou M, Gavriatopoulou M, Roussou M, Tasidou A, Dimopoulos MA (2013) Extensive bone marrow infiltration and abnormal free light chain ratio identifies patients with asymptomatic myeloma at high risk for progression to symptomatic disease. Leukemia 27 (4):947\u0026ndash;953. https://doi.org/10.1038/leu.2012.309\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 15 (12):e538-548. https://doi.org/10.1016/s1470-2045(14)70442-5\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Bao L, Wang Y, Lu M, Chu B, Shi L, Gao S, Fang L, Xiang Q (2020) Hypercalcemia caused by humoral effects and bone damage indicate poor outcomes in newly diagnosed multiple myeloma patients. Cancer Med 9 (23):8962\u0026ndash;8969. https://doi.org/10.1002/cam4.3594\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ho PJ, Moore E, Wellard C, Quach H, Blacklock H, Harrrison SJ, MacDonald EJ, McQuilten ZK, Wood EM, Mollee P, Spencer A (2024) The impact of biomarkers of malignancy (IMWG SLiM criteria) in myeloma in a real-world population: Clinical characteristics, therapy and outcomes from the Australian and New Zealand Myeloma and Related Diseases Registry (ANZ MRDR). Br J Haematol. https://doi.org/10.1111/bjh.19624\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ji M, Wang M, Shih Y-H, Huber J, Fiala MA, Wang R, Sanfilippo KM, Thomas TS, Wang S-Y, Schoen MW, Chang S-H (2024) From criteria to clinic: How updated SLiM CRAB criteria influence multiple myeloma diagnostic activity. Journal of Clinical Oncology 42 (16_suppl):7556\u0026ndash;7556. https://doi.org/10.1200/JCO.2024.42.16_suppl.7556\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e B\u0026auml;uerle T, Hillengass J, Fechtner K, Zechmann CM, Grenacher L, Moehler TM, Christiane H, Barbara W-G, Neben K, Kauczor H-U, Goldschmidt H, Delorme S (2009) Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance: Importance of Whole-Body versus Spinal MR Imaging. Radiology 252 (2):477\u0026ndash;485. https://doi.org/10.1148/radiol.2522081756\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Jung S-H, Koh Y, Kim MK, Kim JS, Moon JH, Min C-K, Yoon DH, Yoon S-S, Lee J-J, Hong CM, Kang K-W, Kwon J, Kim KH, Kim DS, Kim SY, Kim S-H, Kim YR, Do YR, Mun Y-C, Park S-S, Park YH, Shin HJ, Eom H-S, Yoon SE, Hwang SM, Lee WS, Lee M-w, Yi JH, Lee JY, Lee JH, Lee HS, Lim S-N, Lim J, Yhim H-Y, Chang YH, Jo J-C, Cho J, Cho H, Choi YS, Cho Hj, Ahn A, Choi JH, Kim HJ, Kim K (2025) Evidence-based Korean guidelines for the clinical management of multiple myeloma: addressing 12 key clinical questions. BR 60 (0). https://doi.org/10.1007/s44313-025-00055-9\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Ludwig H, Kainz S, Schreder M, Zojer N, Hinke A (2023) SLiM CRAB criteria revisited: temporal trends in prognosis of patients with smoldering multiple myeloma who meet the definition of 'biomarker-defined early multiple myeloma'-a systematic review with meta-analysis. EClinicalMedicine 58:101910. https://doi.org/10.1016/j.eclinm.2023.101910\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Drayson M, Begum G, Basu S, Makkuni S, Dunn J, Barth N, Child JA (2006) Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials. Blood 108 (6):2013\u0026ndash;2019. https://doi.org/10.1182/blood-2006-03-008953\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Rafae A, Malik MN, Abu Zar M, Durer S, Durer C (2018) An Overview of Light Chain Multiple Myeloma: Clinical Characteristics and Rarities, Management Strategies, and Disease Monitoring. Cureus 10 (8):e3148. https://doi.org/10.7759/cureus.3148\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e van Rhee F, Bolejack V, Hollmig K, Pineda-Roman M, Anaissie E, Epstein J, Shaughnessy JD, Jr., Zangari M, Tricot G, Mohiuddin A, Alsayed Y, Woods G, Crowley J, Barlogie B (2007) High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis. Blood 110 (3):827\u0026ndash;832. https://doi.org/10.1182/blood-2007-01-067728\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Snozek CL, Katzmann JA, Kyle RA, Dispenzieri A, Larson DR, Therneau TM, Melton LJ, 3rd, Kumar S, Greipp PR, Clark RJ, Rajkumar SV (2008) Prognostic value of the serum free light chain ratio in newly diagnosed myeloma: proposed incorporation into the international staging system. Leukemia 22 (10):1933\u0026ndash;1937. https://doi.org/10.1038/leu.2008.171\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Garc\u0026iacute;a de Veas Silva JL, Bermudo Guitarte C, Men\u0026eacute;ndez Valladares P, Rojas Noboa JC, Kestler K, Duro Mill\u0026aacute;n R (2016) Prognostic Value of Serum Free Light Chains Measurements in Multiple Myeloma Patients. PLoS One 11 (11):e0166841. https://doi.org/10.1371/journal.pone.0166841\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Bal S, Giri S, Godby KN, Costa LJ (2022) Revisiting the impact of immunoglobulin isotypes in multiple myeloma. Annals of Hematology 101 (4):825\u0026ndash;829. https://doi.org/10.1007/s00277-022-04783-1\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e Kyrtsonis M-C, Vassilakopoulos TP, Kafasi N, Sachanas S, Tzenou T, Papadogiannis A, Galanis Z, Kalpadakis C, Dimou M, Kyriakou E, Angelopoulou MK, Dimopoulou MN, Siakantaris MP, Dimitriadou EM, Kokoris SI, Panayiotidis P, Pangalis GA (2007) Prognostic value of serum free light chain ratio at diagnosis in multiple myeloma. British Journal of Haematology 137 (3):240\u0026ndash;243. https://doi.org/https://doi.org/10.1111/j.1365-2141.2007.06561.x\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Multiple myeloma, CRAB criteria, SLiM criteria, Myeloma-defining events criteria","lastPublishedDoi":"10.21203/rs.3.rs-6884542/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6884542/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eMultiple myeloma (MM) has traditionally been diagnosed on the basis of the CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, and osteolytic Bone lesions), which are used only after permanent end-organ damage has occurred. In 2014, the diagnostic criteria were revised by the International Myeloma Working Group (IMWG) to enable earlier diagnosis, before irreversible organ damage occurs: SLiM criteria (clonal bone marrow plasma cells ≥60%, serum free light chain ratio ≥100, and \u0026gt;1 focal lesion on magnetic resonance imaging) were added to define criteria for myeloma-defining events (MDE; CRAB+SLiM). The aim of this study was to investigate the diagnostic impact of SLiM criteria in real-world clinical practice and explore their relationship with immunoglobulin subgroups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A retrospective review of 257 MM patients diagnosed at Seoul National University Hospital between January 2016 and June 2020 was conducted. The number and percentage of patients meeting MDE criteria were evaluated, and the frequency of each criteria was analyzed by immunoglobulin subgroups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Among the 257 patients, 96.9% met CRAB criteria, while 3.1% met only SLiM criteria. 76.7% met SLiM criteria, with subgroups having different proportions of patients meeting each criterion. The light chain (LC) subgroup tended to have the highest number of MDE criteria met.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The analysis of MDE criteria revealed that the IMWG criteria revised in 2014 led to a slight increase in MM diagnoses (3.2%), from 249 to 257 patients. The addition of SLiM criteria was slightly more helpful in diagnosing MM than traditional CRAB criteria. In subgroup analysis, the LC subgroup tends to meet more CRAB and SLiM criteria than other subgroups, suggesting an association with advanced stage diseases. An increased serum free light chain ratio may indicate underlying plasma cell proliferative disorders.\u003c/p\u003e","manuscriptTitle":"Diagnostic Impact of SLiM Criteria in Multiple Myeloma: A Real-World Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-23 07:13:40","doi":"10.21203/rs.3.rs-6884542/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6d173e23-60f3-4c0a-b969-9b5498824075","owner":[],"postedDate":"June 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-25T12:38:53+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-23 07:13:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6884542","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6884542","identity":"rs-6884542","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}