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EMN recommendations on MM diagnosis and monitoring
Introduction
The classification and differential diagnosis of mono- clonal gammopathies is based on clinical, biological and radiological criteria but remains challenging in certain cases. Multiple myeloma (MM) is the most common malignant gammopathy and is associated with a wide spectrum of signs and symptoms.1 In the past decade, the treatment options for patients with MM have increased considerably. Together with improved supportive care, these new regimens significantly prolong the survival of both younger and older patients.2 The 2014 revision of the diagnostic criteria for MM allows the initiation of treat- ment in patients defined only by biomarkers, annotated as SLIM criteria [bone marrow (BM) infiltration >60%, involved/uninvolved serum free light-chain (SFLC) ratio >100 or >1 focal lesion >5 mm as determined by magnetic resonance imaging (MRI)], without waiting for conven- tional CRAB criteria (hypercalcemia, renal impairment, anemia, bone disease) to occur.3,4 Both the SLIM biomark- er and CRAB criteria are listed in Figure 1. Given the recent evolution in diagnosis and response assessment, members of the European Myeloma Network (EMN) agreed to review and recommend diagnostic and response criteria to allow their discriminating use in daily practice and current care of patients’ .
Methodology
These recommendations were developed by a panel of clinical experts on MM based on evidence of published data through August 2017. Expert consensus was used to suggest recommendations, where sufficient data were lacking. The final recommendations were classified based
on the GRADE criteria,5 which incorporates the strength and quality of evidence (Online Supplementary Table S1). Based on discussions at the 2017 EMN Trialist meeting (Baveno, Italy) guidelines were prepared and circulated among all panel members. The manuscript subsequently underwent revision in three rounds until the EMN experts reached consensus. In line with the guidelines of the International Committee of Medical Journal Editors, authorship was based on active contribution during dis- cussion, writing and revision of the guidelines.
European Myeloma Network recommendations
Diagnostic tools
Blood tests
A defining feature of plasma cell (PC) disorders is the secretion of monoclonal immunoglobulins, often referred to as a monoclonal M-protein, which can be used as a diagnostic marker, but also for the follow-up of the dis- ease. Its heavy- and light-chain components can be identi- fied by immunofixation and further quantified by serum protein electrophoresis and/or a serum free light-chain (SFLC) assay. It should be kept in mind that with persist- ing disease and possible de-differentiation of myeloma cells, the capacity to produce M-proteins may decrease or be completely lost (light-chain escape). In those patients, low M-protein levels, the presence of light chains only, or even complete absence of M-proteins and light chains may be mistaken as an ongoing or evolving response.6
Of note, immunofixation is approximately 10-fold more sensitive than serum protein electrophoresis and is required at diagnosis to characterize the phenotype of the M-protein, and for confirmation of a complete response, which is defined as being immunofixation-negative.7
Figure 1. The differential diagnosis between monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma. The discrimi- nation between these monoclonal gammopathies is based on: (i) the plasma cell infiltration in the bone marrow, (ii) the presence of clinical symptoms related to myeloma disease and (iii) the existence of biomarkers of disease that allow initiation of treatment. MGUS: monoclonal gammopathy of undetermined significance; SMM: smoldering multiple myeloma; MM: multiple myeloma; BM: bone marrow; PC: plasma cells; FLC: free light chain; MRI: magnetic resonance imaging.
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