These individuals must also; lack detectable IgG, IgA, IgD, IgE, or IgM myeloma proteins in sera; have a free κ/λ or λ/κ light chain ratio outside of 0.26 to 1.65 range but less than 100; and/or have no evidence for the presence of any one of the CRAB criteria, amyloidosis, or end organ damage attributable to the myeloma proteins or plasma cells.In a Mayo clinic study of 101 individuals with light chain SMM, the cumulative probability of progression to active multiple myeloma or light-chain amyloidosis in patients with light-chain SMM was 28%, 45%, and 56% after 5, 10, and 15 years, respectively. The major risk factors for progression were the level of urinary excretion of M protein, percentage of bone marrow plasma cells, and immunoparesis (i.e. reduced serum levels of intact immunoglobulins). Paraneoplastic complications
Serious and potentially life-threatening paraneoplastic complications can occur in plasma cell dyscrasias regardless of tumor cell burden, myeloma protein levels, or the presence of other criteria suggesting the dyscrasia has entered a malignant phase. Many of these complications are caused by the tissue-destructive effects of the myeloma proteins, are predictive of a rapidly progressive disease, and require chemotherapeutic or other treatments directed at lowering the burden of the myeloma protein-producing cells. The serious paraneoplasitic diseases that complicate the plasma cell dyscrasias and may require such treatments include the following. Amyloidosis
Amyloidosis is a general term for a protein misfolding syndrome that involves the deposition of a low molecular weight beta-pleated sheet-containing protein in extracellular tissues.
a Glomerular filtration rate of <40; and c) biopsy confirmed or suspicion of cast nephropathy, glomerulonephritis, of other morphological expressions of clonal immunoglobulin-induced kidney injury. Increased excretion of a urinary monoclonal light chain (typically >0.5 gram/day), which suggests the presence of a particularly severe form of kidney injury (myeloma cast nephropathy), supports but is not a requirement for the diagnosis of MGRS. The disorder can also be caused by a monoclonal immunoglobulin that acts as an autoantibody that activates the blood complement system to cause complement-related kidney injury. This form of MGRS is usually associated with other syndromes like glomerulopathy associated with a monoclonal immunoglobulin or C4 dense deposit disease associated with a monoclonal immunoglobulin. Diagnosis depends or identifying these other syndromes and the identification of complement components on kidney biopsy. Regardless of the exact pathophysiology causing monoclonal immunoglobulin-induced kidney injury, MGRS has a greater morbidity and mortality than other forms of MGUS. Since renal dysfunction usually improves with therapy directed at the underlying plasma cell dyscrasia, MGRS may warrant treatment even when other parameters of plasma cell dyscrasia severity (e.g. low levels of serum monoclonal immunoglobulin and bone marrow plasma cells) suggest the presence of minimal, non-malignant disease. Smoldering multiple myeloma stage
Smoldering multiple myeloma or SMM (also termed smoldering myeloma) is the next stage following MGUS in the spectrum of plasma cell dyscrasias. While still considered a pre-malignant condition, its chances of progressing to a malignant plasma cell dyscrasia are generally greater than that for MGUS.