Monoclonal gammopathy of undetermined significance with low and high risk degree: outputs from analyses RMG of register of Czech myeloma group for practice

Czech version

Authors: V. Sandecká ¹; R. Hájek ²; Z. Adam ¹; I. Špička ³; V. Ščudla ⁴; E. Gregora ⁵; J. Radocha ⁶; L. Walterová ⁷; P. Kessler ⁸; D. Adamová ⁹; K. Valentová ¹⁰; I. Vonke ¹¹; L. Ulmanová ¹²; D. Starostka ¹³; M. Wróbel ¹⁴; L. Brožová ¹⁵; J. Jarkovský ¹⁵; A. Mikulášová ¹⁶; L. Říhová ¹⁷; M. Almaši ¹⁷; S. Ševčíková ¹⁶; M. Krejčí ¹; J. Straub ³; J. Minařík ⁴; P. Pavlíček ⁵; L. Pour ¹; P. Všianská ¹⁷; S. Okutabe ¹⁶; M. Penka ¹⁷; V. Maisnar ^6*
Authors‘ workplace: Interní hematologická a onkologická klinika FN Brno ¹; Klinika hematoonkologie, FN Ostrava ²; I. Interní klinika - klinika hematologie, VFN Praha ³; Hemato-onkologická klinika, FN Olomouc ⁴; Interní hematologická klinika, FN Královské Vinohrady Praha ⁵; IV. interní hematologická klinika, FN Hradec Králové ⁶; Oddělení klinické hematologie, Krajská nemocnice Liberec ⁷; Oddělení hematologie a transfuziologie, Nemocnice Pelhřimov ⁸; Hematologicko-transfúzní oddělení, Slezská nemocnice v Opavě ⁹; Oddělení klinické hematologie, Thomayerova nemocnice Praha ¹⁰; Oddělení klinické hematologie, Nemocnice České Budějovice ¹¹; Hematologicko-transfúzní oddělení, Klaudiánova nemocnice Mladá Boleslav ¹²; Oddělení klinické hematologie, Nemocnice s poliklinikou Havířov ¹³; Oddělení klinické hematologie komlexního onkologického centra Nový Jičín ¹⁴; Institut biostatistiky a analýz, Masarykova univerzita Brno ¹⁵; Babak Myeloma Group, Katedra patologické fyziologie, Masarykova Univerzita Brno ¹⁶; Oddělení klinické hematologie, FN Brno ¹⁷
Published in: Klin. Biochem. Metab., 23 (44), 2015, No. 2, p. 53-59

* v zastoupení České myelomové skupiny

Overview

Aim:
The primary end point was to estimate the cumulative risk of hematologic disorders occurring during the follow-up of our cohort. The secondary end points were: to validate known clinical models suggested by the Mayo Clinic group and the Spanish PETHEMA group for the risk of progression from MGUS to MM or related malignancies and to establish a new risk model by the Czech Myeloma Group (CMG model) with better prediction of low-risk MGUS group.

Results:
1887 MGUS persons were followed with median 4 years. Malignancies developed in 8.6 % (162/1887) cases; MM occurred in 77.2 % (125/162) of persons. The risk of progression was 1.5 % at 1 year, 7.6 % at 5 years and 16.5 % at 10 years after diagnosis. The key predictors factors of progression were as follows: age ≥ 69 years, serum M- protein concentration ≥ 15 g/L, bone marrow plasma cells > 5 %, pathological sFLC ratio (< 0.26 or >1.65), immunoparesis of polyclonal immunoglobulins and levels of serum hemoglobin at baseline < 120 g/L . Distribution of MGUS persons according to risk groups based on the Mayo Clinic model confirmed predictive power of Mayo Clinic model based on our data although isotype of M- protein was not found as independent predictor. At 10 years, no-risk group had 4.9 % risk of progression compared to 16.3 %, 24.6 %, and 54.9 % in groups with 1, 2 or 3 risk factors, respectively (p< 0.001). Immunoparesis instead of DNA aneuploidy was used together with the presence of abnormal plasma cells (aPCs) to validate the modified PETHEMA model. The rates of progression at 2 years were 1.6 %, 8.1 % and 28.0 % for groups with neither, one or both risk factors, respectively (p< 0.001). Based on the 5 parameters with independent predictive value in the univariate analysis we proposed a new CMG model. At 10 years, risk group with 4-5 risk factors had 1.6 %, 16.9 %, 22.9 %, 39.4 % and 52.3 %, retrospectively (p< 0.001).

Conclusion:
In the large cohort of MGUS persons, we confirmed validity of previously considered clinical models for the risk of progression from MGUS to MM by the Mayo Clinic group and the Spanish PETHEMA group (model used for SMM). New CMG model for the risk of progression from MGUS to MM or related malignancies was established with an advantage for better identification of MGUS persons at low risk (87 % of persons with risk of progression below 10 % in 5 years) as well as few persons at the highest risk of progression.

Keywords:
multiple myeloma, monoclonal gammopathy of undetermined significance, risk factors.

Sources

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Clinical Biochemistry and Metabolism

2015 Issue 2