Onkologie 2022: 16(Suppl.B): 33-56

Monoclonal gammopathy of undetermined signifikace (MGUS and monoclonal gammopathy of clinical significance (MGCS)

prof. MUDr. Zdeněk Adam, CSc.¹, MUDr. Ing. David Zeman, Ph.D.², prof. MUDr. Luděk Pour, Ph.D.¹, prof. MUDr. Marta Krejčí, Ph.D.¹, MUDr. Soňa Štěpánková, Ph.D.³, prof. MUDr. Vladimír Vašků, Ph.D.⁴, doc. MUDr. Eva Vlčková, Ph.D.⁵, doc. MUDr. Zdeněk Řehák, Ph.D.⁶, MUDr. Renata Koukalová, Ph.D.⁶, MUDr. Gabriela Romanová⁷, MUDr. Zuzana Adamová, Ph.D.⁸, MUDr. Zdeněk Král, CSc.¹, MUDr. Viera Sandecká, Ph.D.¹

¹ Interní hematologická a onkologická klinika, LF MU a FN, Brno

² Ústav laboratorní medicíny, Oddělení klinické biochemie, LF MU a FN, Brno

³ Centrum kardiovaskulární a transplantační chirurgie, LF MU a FN u svaté Anny, Brno

⁴ Dermatovenerologická klinika LF MU a FN u svaté Anny, Brno

⁵ Neurologická klinika, LF MU a FN, Brno

⁶ Oddělení nukleární medicíny, Masarykův onkologický ústav, Brno

⁷ Oddělení klinické hematologie - specializovaná ambulance pro koagulační poruchy, LF MU a FN, Brno

⁸ Chirurgické oddělení Nemocnice Frýdek Místek a Chirurgické oddělení Vsetínské nemocnice

Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a monoclonal protein (M-protein) without evidence of multiple myeloma (MM), Waldenstrom‘s macroglobulinemia (WM), amyloidosis (AL), or a related plasma cell proliferative disorder. MGUS is found in approximately 3 % of persons > 70 years of age and in about 1 % of those > 50 years old. At Mayo Clinic from 1960 through 1994, the risk of progression was 1 % per year. This risk of progression continued even after  of a stable M-protein. The risk for developing MM, WM, or AL was increased 25-fold, 46-fold, and 8.4-fold, respectively. 

The concentration of the serum M-protein, abnormal serum free light-chain ratio, and the presence an immunoglobulin (Ig)M or an IgA M-protein were risk factors for progression. The presence of a urine M-protein was not a risk factor for disease progression. Variants of MGUS consist of IgM MGUS, biclonal gammopathies, triclonal gammopathies, idiopathic Bence Jones (light-chain) proteinuria, and IgD MGUS. Monoclonal gammopathy of undetermined significance may be associated with many disorders, including lymphoproliferative diseases, leukemia, von Willebrand‘s disease, connective tissue diseases, and neurologic disorders. MGUS results from a small and/or quiescent secreting B-cell clone, is completely asymptomatic, and requires regular monitoring only. Sometimes, although plasma cell are quiescent and not requiring any treatment per se, the clone is associated with potentially severe organ damage due to the toxicity of the monoclonal immunoglobulin or to other mechanisms. The latter situation is increasingly observed but still poorly recognized and frequently undertreated, although it often requires rapid specific intervention to preserve involved organ function. To improve early recognition and management of these small B-cell clone-related disorders, autors from Mayo Clinic proposed to introduce the concept of monoclonal gammopathy of clinical significance (MGCS). This report identifies the spectrum of MGCSs that are classified according to mechanisms of tissue injury. It highlights the diversity of these disorders for which diagnosis and treatment are often challenging in clinical practice and require a multidisciplinary approach. Principles of management, including main diagnostic and therapeutic procedures, are also described. Importantly, efficient control of the underlying B-cell clone usually results in organ improvement. Currently, it relies mainly on chemotherapy and other anti-B-cell/plasma cell agents, which should aim the best hematological response. Combinations of daratumumab with other anti-myeloma drugs may be best solution. High immunomodulatory dosis of IVIGs can help in failure of the anti-plasma cell therapy.

Keywords: monoclonal gammopathy of undetermined significance, monoclonal gammopathy of clinical significance, daratumumab, IVIG.

Published: October 14, 2022  Show citation