Behind the Scenes Videos

Check out these bonus scenes from Core IM’s interview with Dr. Vincent Rajkumar, an expert hematologist/oncologist and researcher in the field of Monoclonal Gammopathies. 

Interpreting the SPEP / UPEP / FLC / Immunofixation Tests

Key Points:

  • Plasma cell disorders result from a monoclonal proliferation of plasma cells that typically secrete large amounts of an antibody (the “M protein”)
  • The serum tests:
  • SPEP reports an “M-spike” representing the amount and size of monoclonal protein
  • Immunofixation reports the type of protein being secreted (IgG, IgM, etc)
  • Free Light Chain Assay reports the amounts and ratios of FLCs,
  • A normal K:L ratio is 0.26 -1.65, but as long as the ratio is less than 8, this is not concerning provided there are no other features suggesting myeloma
  • Renal failure and systemic inflammation can cause mild increases in the K:L ratio
  • This is the most sensitive test
  • When ordered together SPEP/Immunofixation/ FLC assay is 98% sensitive
  • MGUS that requires work-up with a bone marrow biopsy if they DO NOT fall into the following categories:
      • IgG MGUS with monoclonal less than 1.5 and normal K:L ratio
      • IgM MGUS in most cases
      • Light chain only MGUS
    • In these patients, just repeat the SPEP, immunofixation, and FLC ratio in 6 months to confirm stability
    • However, if there are features that worry you about the patient, regardless of the SPEP results, it is not wrong to obtain a bone marrow biopsy to rule out myeloma

When to Consider Monoclonal Gammopathies 

Key Points:

  • Patient has characteristics of Myeloma:
    • Lytic bone lesions
    • Renal failure + hypercalcemia, granular casts, high urine protein
    • Ca is low in CKD + urinary dipstick measures albumin, NOT total protein! 
    • Unexplained normochromic, normocytic anemia
  • Patient has characteristics of Amyloid:
    • Hemihypertrophy, specific neuropathies, etc.
  • Patient has characteristics of Waldenstrom:
    • Unexplained hyperviscocity
  • All patients with findings other than small IgG/IgM MGUS warrant referral to hematology for bone marrow biopsy and skeletal staging

Differentiating MGUS, Smoldering Myeloma, and Multiple Myeloma

Key Points:

  • Diagnostic criteria as of 2014 makes diagnosis of MM more sensitive; aiming to identify and treat patients who would develop CRAB features in next 1-2 years
  • Multiple myeloma (MM): clonal bone marrow plasma cells + “myeloma defining event”
  • MM defining event:
    • CRAB feature attributable to plasma cell disorder OR
    • less than 60% plasma cells on bone marrow biopsy OR
    • light chain ratio greater than 100 with significant monoclonal protein on UPEP OR
    • less than 1 focal lesion on MRI
  • MGUS: less than 3g M-spike and less than 10% plasma cells on bone marrow biopsy (if performed)
  • Smoldering Myeloma: less than 3g M-spike or 10% – 60% plasma cells in bone marrow biopsy

Initial Treatment of Monoclonal Gammopathies 

Key Points:

  • MGUS: 1% of patients progress annually; focus on their other medical comorbidities
  • First line treatments for Smoldering / Multiple Myeloma: Lenalidomide, Bortezomib, Daratumumb
  • Daratumumab decreases antibody production by targeting
  • CD 38 on plasma cells
    • Common adverse effects:
      • Lenalidomide can cause peripheral neuropathy, thrombosis
    • Bortezomib can cause peripheral neuropathy 

What Are Monoclonal Gammopathies of Clinical Significance?

Key Points: 

  • MGCS is a MGUS-related condition in which the monoclonal protein causes clinical symptoms due to its physiological target.
  • e.g. a monoclonal antibody targeting neurons causing neuropathy
  • MGCS is a pre-malignant condition, differing only from MGUS by the presence of symptoms.
  • MGCS can present in numerous ways including neuropathy, glomerulonephritis, dermatitis, amyloidosis, cryoglobulinemia, and cold agglutinin disease.

Full Episode

MGUS to Multiple Myeloma Diagnostics and Counseling: 5 Pearls Segment