From the Guidelines
The recommended screening approach for multiple myeloma and amyloidosis involves a stepwise evaluation starting with serum and urine tests, including a complete blood count, comprehensive metabolic panel, serum protein electrophoresis with immunofixation, serum free light chain assay, and 24-hour urine protein electrophoresis with immunofixation, as outlined in the most recent guidelines 1.
Initial Screening Tests
The initial screening tests for multiple myeloma and amyloidosis should include:
- Complete blood count
- Comprehensive metabolic panel
- Serum protein electrophoresis with immunofixation
- Serum free light chain assay
- 24-hour urine protein electrophoresis with immunofixation These tests can detect the presence of monoclonal proteins (M-proteins) that characterize these disorders, and are particularly important for individuals over 60 years of age, those with unexplained kidney disease, heart failure with preserved ejection fraction, peripheral neuropathy, or those with a family history of these conditions 1.
Further Evaluation
If screening tests are positive, further evaluation with:
- Bone marrow biopsy
- Skeletal survey or advanced imaging (low-dose CT, MRI, or PET-CT)
- Organ-specific testing based on symptoms is warranted. For amyloidosis specifically, tissue biopsy of affected organs with Congo red staining is often necessary for definitive diagnosis, and mass spectrometry-based analysis (LC-MS/MS) of the biopsy is the gold standard for tissue diagnosis 1.
Importance of Early Detection
Early detection is crucial as both conditions can cause significant organ damage if left untreated, and modern treatments can significantly improve outcomes when initiated before advanced organ involvement occurs. The serum free light chain assay is useful to monitor disease response and progression in a proportion of patients with nonsecretory myeloma, and the FLC ratio is required for documenting stringent complete response (CR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria 1.
From the Research
Screening Approaches for Multiple Myeloma and Amyloidosis
- The recommended screening approach for multiple myeloma and amyloidosis involves a combination of serum protein electrophoresis (SPE) and serum free light chain (SFLC) measurements, along with clinical information 2.
- Mass spectrometry (MS) is also emerging as a useful tool for evaluating monoclonal proteins in multiple myeloma and related disorders, with immune-enrichment of immunoglobulins coupled to intact light chain MALDI-TOF MS showing equivalent performance to immunofixation electrophoresis (IFE) 3.
- Serum protein electrophoresis and free light chain assay of the serum can detect the precursors of multiple myeloma, such as monoclonal gammopathy of undetermined significance and smoldering multiple myeloma, raising the question of whether population-based screening could detect multiple myeloma at an asymptomatic stage 4.
- A serum-based algorithm of SPE and SFLC has been adopted by many laboratories as a first-line screen in patients with suspected monoclonal gammopathies, due to the limited sensitivity and practical constraints of urine analysis 5.
Diagnostic Criteria and Interpretation
- Serum protein electrophoresis separates proteins based on their physical properties, and the subsets of these proteins are used in interpreting the results, with a homogeneous spike-like peak in a focal region of the gamma-globulin zone indicating a monoclonal gammopathy 6.
- The quantity of M protein, the results of bone marrow biopsy, and other characteristics can help differentiate multiple myeloma from other causes of monoclonal gammopathy 6.
- Monoclonal gammopathies are associated with a clonal process that is malignant or potentially malignant, including multiple myeloma, Waldenstrom's macroglobulinemia, solitary plasmacytoma, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance, plasma cell leukemia, heavy chain disease, and amyloidosis 6.
Current Limitations and Future Directions
- While screening for multiple myeloma and its precursors may lead to a paradigm shift in the care of patients with multiple myeloma, critical scientific questions need to be answered before screening of healthy individuals can be recommended, including the benefits and harms of screening and the lack of a defined target population 4.
- Ongoing studies may fill these critical gaps in the literature, but their results are still pending 4.