Sethi et al.1 provide a comprehensive review of monoclonal Ig (MIg)–associated renal diseases and elucidate monoclonal gammopathy of renal significance (MGRS). In MGRS, the clonal plasma cell or B cell proliferation is too small to meet the criteria of multiple myeloma (MM) or symptomatic lymphoma, and thus, it does not warrant immediate hematologic treatment. This new term has fulfilled a clinical need to distinguish monoclonal gammopathy of undetermined significance from MGRS and paved the way for an onconephrologic approach using clone-directed therapies in thoroughly assessed patients with MGRS with the objective to preserve renal function.2,3
MGRS caused by plasma cells is defined as <10% bone marrow plasma cells (BMPCs), <3 g/dl of M protein, and the presence of renal lesions without any other myeloma-defining events.1 As with MGRS, patients with smoldering myeloma (SMM) are asymptomatic but have higher MIg levels and BMPCs. In 2014, the International Myeloma Working Group (IMWG) updated the diagnostic criteria of MM to include BMPCs>60% and serum free light chain ratio >100 as myeloma-defining events. Thus, the revised definition of SMM is an intermediate stage between monoclonal gammopathy of undetermined significance and MM with BMPCs of 10%–60% and/or serum MIg >3g/dl.4 The standard of care in SMM is observation until progression to MM or enrolment in a clinical trial. For patients with SMM who have MGRS renal lesions, guidance is lacking. The IMWG recommends that MGRS renal lesions should not be regarded as myeloma-defining events leading to MM diagnosis. With patients with SMM excluded from the MGRS group and not warranting immediate myeloma-type management, a clinicopathologic gap is created. In our center, during 2006–2017, we identified 163 of 4374 (3.7%) native biopsies with MIg-associated lesions. After exclusion of MM, lymphoma, and Light-chain (AL) amyloidosis, 40 patients had an MGRS-type renal lesion. Of these patients, 30 had a bone marrow biopsy. Eight of 30 (27%) patients had SMM (BMPCs=10%–60%). Therefore, the number of patients falling in this clinicopathologic gap is quite substantial in our experience.
SMM with MGRS-type lesions is not uncommon, and the best therapeutic approach remains to be defined. Although it is reasonable to adopt treatment strategies similar to MGRS, we believe that SMM of renal significance merits more attention in the MIg-associated renal diseases nomenclature. This will increase awareness for renal screening in SMM and improve study design when evaluating new approaches to the full spectrum of MIg-associated diseases.
Disclosures
None.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
References
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