P903: clinical utility of monoclonal gammopathy screening in the evaluation of peripheral neuropathy

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Screening for monoclonal gammopathy (MG) is routinely performed in the evaluation of peripheral neuropathy. While certain MGs may be associated with neuropathy, for example light chain amyloidosis (AL), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome, and Waldenstrὂm macroglobulinemia (WM), these are rare conditions (<10/million/year combined). In contrast, multiple myeloma (MM; 7/100,000/year) and monoclonal gammopathy of undetermined significance (MGUS; prevalence of 8% among age >50 years) are more common, but rarely cause neuropathy. Therefore, abnormal results from MG screening may be unrelated to patient symptoms and result in financial and psychological harm. Limited data exist to guide clinicians regarding the utility of MG testing for neuropathy. Aims: This study aims to describe the clinical utility of MG screening during the evaluation of neuropathy. Methods: We retrospectively reviewed the charts of patients screened in 2021 for MG as part of the workup for peripheral neuropathy at Mayo Clinic. Patients with a previously diagnosed MG were excluded. MG testing included serum protein electrophoresis and free light chain assessments. In patients with MG, the following data were extracted: hemoglobin, calcium, creatinine, eGFR, and the final hematologic diagnosis related to the monoclonal protein. We followed the patients longitudinally to determine the attributed etiology of peripheral neuropathy. Patients were divided into those with a lymphoplasmacytic neoplasm and those with MGUS alone. Patients diagnosed with MGUS were stratified based upon the etiology of their neuropathy after workup was completed to assess the clinical utility of testing. The routine MG screenings which found a new diagnosis of lymphoplasmacytic neoplasm were deemed to be of clinical utility regardless of neuropathy etiology. Results: Among the 1436 patients with neuropathy who were screened for MG, 150 (10.4%) were found to have a newly diagnosed MG. Of the latter, 148 (98.6%) were MGUS and the other 2 (1.4%) were MM (1) and POEMS (1). Only 12 (0.83%) patients screened for MG were ultimately found to have neuropathy caused by MG. The types of MG felt to be responsible for the neuropathy were MGUS (5 IgM, 4 IgG, and 1 IgM/IgG biclonal), MM (1), and POEMS (1). Common causes of neuropathy in patients with newly diagnosed with MG were; hereditary/genetic conditions (25; 16.6%), diabetes mellitus or hyperglycemia (23;15.3%), mechanical/radiculopathy (13; 8.6%), CIDP (9; 6%), alcohol (8; 5.3%), autoimmune-related (6; 4%), and idiopathic (39; 26%). Among the 2 patients with newly diagnosed lymphoplasmacytic neoplasms, one presented with the Sign of Leser Trelat and lytic bone lesions on imaging. The other patient presented with symptoms consistent with POEMS including edema, hypothyroidism, and sclerotic bone lesions on imaging. Among the 12 patients diagnosed with MG associated neuropathy, 4 (33%) were placed on therapy for their MG. Therapies included lenalidomide, rituximab, and IVIG. Summary/Conclusion: In the evaluation of peripheral neuropathy, routine MG screening has low clinical utility. Less than 1 in 100 patients were found to have a MG associated neuropathy. Furthermore, only 3 in 1000 patients received MG-directed therapy. Given the cost to healthcare and potential psychological harm to the patient of incidental MG diagnosis, further study is warranted to guide clinicians and limit the ordering of MG testing to individuals who are most likely to derive benefit. Keywords: Myeloma, Monoclonal gammopathy, Multiple myeloma, MGUS