A collection of clincally important insights in myeloma and MGUS – Vincent Rajkumar
1/ Serum protein electrophoresis may underestimate the true size of the M protein when the level is too high. The gel saturates. So go by the quantitative IgG/IgA level to get a better estimate of M spike size.
2/ Serum protein electrophoresis may give incorrect value for the true size of the M protein in IgA myeloma because IgA forms dimers and trimers. Follow the IgA level also to get a better estimate of true M spike size.
3/ Myeloma can cause renal failure through multiple mechanisms. But only light chain cast nephropathy counts as a myeloma defining event. The others can be seen with MGUS (premalignancy) also.
4/ In suspected newly diagnosed myeloma presenting with acute renal failure: if the serum FLC level is >150mg/dl it’s presumed light chain cast nephropathy. Renal biopsy not needed in most situations.
5/ Light chain cast nephropathy and light chain deposition disease (LCDD) are two entirely different diseases. LCDD is a glomerular problem that causes nephrotic syndrome and can occur with MGUS or MM.
6/ DSS, ISS, RISS etc are prognostic systems. They are best used for counseling and for comparing trials. These systems mix host factors, tumor burden and/or biology to predict prognosis. But because they mix them up, they are not useful in picking therapy.
7/ To pick therapy to overcome aggressive biology you need to use biomarkers associated with disease aggressiveness.
8/ Once renal failure occurs due to cast nephropathy in myeloma, even if reversed prognosis doesn’t quite return to normal. Better to prevent renal failure in the first place.
9/ Post radiation to a plasmacytoma if the mass continues to be same size and shows persistent uptake it is more likely residual scar or amyloid than viable malignancy. Monitor with imaging and avoid reflexive urge to give more therapy.
10/ Circulating plasma cells can be detected in almost all patients with myeloma by flow. But when you see them on regular CBC differential/smear the level is too high. And even a small % is sufficient to consider as plasma cell leukemia.
11/ Pleural effusion, pericardial effusion or liver that is involved with myeloma cells has same connotation as plasma cell leukemia in terms of severity and seriousness and probably biology.
12/ CNS involvement is uncommon and hard to treat when it occurs. I have not treated CNS involvement with myeloma successfully. So it’s one of those situations where although we may want to try heroic things, the track record is not good. We need better data.
13/ After stem cell transplant a subset of patients develop a secondary MGUS with a new M protein type. This is not something to worry about. It is usually associated with better prognosis. And usually resolves in a year or so.
14/ Although the FLC assay is great for monitoring light chain levels, we still recommend checking UPEP once every 6 months or so to detect other problems like albuminuria from amyloid or LCDD.
15/ The reference FLC levels and ratio were first established using normal young healthy controls. We now know the ranges will be higher in older people and in renal failure. So borderline abnormalities don’t signify MGUS in absence of M protein on immunofixation.
16/ Don’t forget alkylator based combinations in relapsed myeloma: VCd, KCd etc. Alkylators work in myeloma and many patients haven’t seen alkylators at all or only as part of stem cell transplant. Some patients can get enduring response.
17/ MGUS neuropathy is mainly a clinical diagnosis. IgM MGUS neuropathy starts distal, it’s mainly sensory, demyelinating. Slowly moves proximal. IgG, IgA MGUS neuropathy is not a diagnosis I make often. It’s rare. It’s CIDP like, with simultaneous proximal & distal involvement
Source: Vincent Rajkumar/Twitter