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Algorithm for the evaluation of suspected clonal plasma cell disorder

Algorithm for the evaluation of suspected clonal plasma cell disorder

AL: amyloid light-chain; CRAB: hypercalcemia, renal insufficiency, anemia, bone lesions; CT: computed tomography; eGFR: estimated glomerular filtration rate; FISH: fluorescence in situ hybridization; FLC: free light chain; IgA: immunoglobulin A; IgD: immunoglobulin D; IgG: immunoglobulin G; IgM: immunoglobulin M; LDH: lactate dehydrogenase; MGUS: monoclonal gammopathy of undetermined significance; MM: multiple myeloma; MRI: magnetic resonance imaging; PET: positron emission tomography; SLiM: ≥60% clonal plasma cells in the bone marrow; involved/uninvolved FLC ratio of 100 or more (provided involved FLC level is at least 100 mg/L); MRI with more than one focal lesion (involving bone or bone marrow); SPEP: serum protein electrophoresis.

* Patients with solitary plasmacytoma, non-secretory multiple myeloma, and rare cases of AL amyloidosis may not have detectable M protein or abnormal serum FLC assay.

¶ Imaging should be performed using whole body low dose CT, whole body PET/CT, whole body MRI, or MRI of the spine and pelvis (depending upon availability and institutional preference). Biopsy of the bone lesion should be performed if a solitary lesion is detected or if the cause of the lesion is unclear. Bone imaging may be omitted for patients with IgM M protein and no clinical concern for bone lesions or myeloma.

Δ When interpreting the FLC assay in clinical practice, clinicians should refer to the normal reference range specified by the laboratory reporting the result. Reference ranges differ between assays from different manufacturers and are dependent upon the instrument used for measurement. Reference ranges may also be adjusted for the patient's estimated glomerular filtration rate[1]; For the serum FLC assay developed by The Binding Site:
  • eGFR ≥60 mL/min/1.73 m2
    • FLC ratio 0.26 to 1.65
    • Serum free kappa 3.3 to 19.4 mg/L
    • Serum free lambda 5.7 to 26.3 mg/L
  • eGFR 45 to 59 mL/min/1.73 m2
    • FLC ratio 0.46 to 2.62
    • Serum free kappa 7.8 to 83.6 mg/L
    • Serum free lambda 7.3 to 65.1 mg/L
  • eGFR 30 to 44 mL/min/1.73 m2
    • FLC ratio 0.48 to 3.38
    • Serum free kappa 8.8 to 103.3 mg/L
    • Serum free lambda 8.2 to 73.2 mg/L
  • eGFR <30 mL/min/1.73 m2
    • FLC ratio 0.54 to 3.30
    • Serum free kappa 11.7 to 265 mg/L
    • Serum free lambda 12.6 to 150.9 mg/L
Reference:
  1. Long TE, Indridason OS, Palsson R, et al. Defining new reference intervals for serum free light chains in individuals with chronic kidney disease: Results of the iStopMM study. Blood Cancer J 2022; 12:133.
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