Mark Kristjanson ASA 2020 RBC Convention Centre April 23 – 25, 2020

Thanks owed to Drs. Emily Rimmer & Arvand Barghi CFPC CoI Templates: Slide 1 – used in Faculty presentation only.

Faculty/Presenter Disclosure  Faculty: Mark Kristjanson

 Relationships with financial sponsors:  NO CONFLICTS TO DECLARE Monoclonal proteins Free Light Chains! Serum Protein Electrophoresis Serum Protein Electrophoresis Immunofixation Electrophoresis (IPE)  SPEP tells you the amount of an M-protein  If an M-protein is present on SPEP, IPE is added  IPE tells you the particular type (e.g. IgG kappa) When to Order SPEP and FLC:

• Unexplained anemia • Heavy proteinuria or Bence Jones • Osteopenia, osteolytic lesions proteinuria • Spontaneous fractures • Hypercalcemia with low PTH • Renal insufficiency with bland urinary • Hypergammaglobulinemia sediment • Immunoglobulin deficiency Result of Result of SPEP FLC

Polyclonal Oligoclonal Elevated light chain (kappa or Elevated light (Reactive) (usually Monoclonal lambda) AND abnormal ratio chains with reactive) (monoclonal) normal ratio (reactive)

Investigate other Repeat SPEP in 6 causes: months if See Monoclonal Protein Algorithm Investigate other clinically causes including • Liver disease indicated (see renal failure • Connective tissue above) (Ratio up to 3 can disease be normal in • Infection chronic kidney • Inflammation disease) Monoclonal Protein identified on SPEP or FLC

Are CRAB features present?** Assess for CRAB features, order: 2+ • C Ca > 2.8 • CBC • R renal :Creatinine > 177 or • Creatinine Refer to eGFR < 40 ml/min • Ca2+ Hematology yes • A anemia: Hemoglobin less than • For IgM subtype, assess for 100 g/L lymphadenopathy and • B bone: lytic bone lesions splenomegaly

**attributable to plasma disorder No CRAB features

Are there any of the following high-risk features? Order skeletal • Non-IgG, Non-IgM monoclonal yes survey protein • Monoclonal protein > 15 g/L • Kappa or Lambda FLC > 100 mg/L • FLC ratio < 0.125 or > 8.0

no

See MGUS follow-up algorithm MGUS follow up

Repeat CBC, calcium, creatinine, SPEP, and FLC in 6 months

Possible progression: • M-protein increase by 5 g/L Refer to • FLC increase by 100 mg/L Stable • FLC ratio becomes < Hematology 0.125 or > 8 • New onset CRAB features

Repeat CBC, calcium, creatinine, SPEP, and FLC annually More about SPEP and IFE

In Manitoba, DSM performs a “screening gel” on • all first encounters • samples referred in from Dynacare • samples from patients whose previous work up has been negative • or has shown an oligoclonal or polyclonal (but not a monoclonal) gammopathy More about SPEP and IFE

• The screening gel is a quick gel • then stained with a serum that contains antibodies to: IgG, IgM, IgA, K and L. • If it is positive it tells you there is an M-band but doesn’t tell you what kind or how much • If the screen is negative, there is no M-protein. More about SPEP and IFE

• See how the band is present on sample 4 and 5? These go on to have a standard SPEP and IFE. • Sample 1-3, and 6 are negative More about SPEP and IFE

A standard SPEP (vs. the “screening gel”) spreads out the proteins, like in this normal SPEP:

No IFE is needed when there is no M-protein More about SPEP and IFE

If the SPEP looks like this: Immunofixation electrophoresis (IFE) is done to characterise the M-protein SPEP & FLC indications

 clinical suspicion for a condition associated with an M- protein.  screening test should include SPEP and FLC SPEP & FLC indications  Unexplained anemia  Back pain: persistent & unexplained; or  Osteopenia, osteolytic lesions, spontaneous fractures  Renal insufficiency with bland urinary sediment  Heavy proteinuria or Bence Jones proteinuria  Hypercalcemia with normal (or low) PTH SPEP & FLC indications  Hypergammaglobulinemia  Immunoglobulin deficiency  Unexplained peripheral neuropathy  Recurrent infections  Elevated ESR or serum viscosity  Peripheral blood smear showing rouleaux Osteoporosis Canada says: if osteoporosis (i.e. T-score ≤ −2.5), then Subtype IgG, IgA, IgD Kappa or Lamdba • M-protein concentration* • CBC, creatinine, Ca2+ (to evaluate CRAB symptoms) • Serum free light chain ratio (FLCR) • U/A to assess proteinuria

❑*if SPEP shows M-protein, serum immunofixation electrophoresis is paired with the SPEP. ❑SPEP tells you the concentration and the IFE tells you the subtype. CRAB symptoms*

 C – Ca++ >2.8  R – creatinine >177 umol/L or GFR <40mL/min  A – hemoglobin <100g/L or 20g/L below normal  B – lytic lesions *Attributable to plasma cell disorder Subtype IgM

Same tests, and • Consider CT chest / abdomen / pelvis to assess for lymphadenopathy • If any of the following present: ✓ lymphadenopathy OR ✓ splenomegaly OR ✓ anemia (hgb <105g/L) Refer to Hematology re: ? Waldentrom’s Subtype IgM  Not everyone who has an IgM M-protein needs a CT scan  If IgM < 15 with normal CBC and physical exam, do not need CT imaging or referral  Manage as low risk MGUS Low Risk MGUS

If:  IgG M-protein <15g/L  Normal FLCR  No CRAB

Then:  Low Risk MGUS Low Risk MGUS

 Repeat SPEP in 6 months;  Plus Hb, Cr, Ca++;  if stable, then q1-2 years or with CRAB symptoms MGUS  IgA, IgD < 15 g/L  No CRAB  Risk of progression to myeloma ~1%/year  Refer non-urgently to Hematology Monoclonal protein If:  IgG M-protein >15 g/L  Abnormal FLCR  Or CRAB feature(s) present Then:  Order Skeletal Survey  Refer to Hematology Monoclonal protein (any amount)  Skeletal survey abnormal OR  CRAB symptoms

 Multiple myeloma suspected  Refer to Hematology urgently Monoclonal Protein > 15 g/L If:  Skeletal survey normal AND  No other CRAB symptoms Then:  Suspect smoldering myeloma  Routine referral to Hematology MONOCLONAL PROTEIN INVESTIGATION  Date effective: March 16, 2020  Background Information:  In an effort to align laboratory practice and international guidelines, changes to the testing algorithm for monoclonal protein investigations will be implemented on March 16, 2020.  The International Myeloma Working Group guidelines recommend: MONOCLONAL PROTEIN INVESTIGATION

 1. Serum Free Light Chain quantitation in combination with serum protein electrophoresis (SPE) and serum immunofixation electrophoresis (IFE) in the initial diagnostic workup (screen) for pathological monoclonal plasma cell proliferative disorders.  2. When performed at screening, Serum Free Light Chains can replace the 24hr urine protein IFE for all diagnoses except amyloidosis. However, once a diagnosis of monoclonal gammopathy is made, the 24hr urine protein IFE should be done. MONOCLONAL PROTEIN INVESTIGATION

 Change in Test Procedure:  1. All Serum Protein Electrophoresis (PE) orders, both initial and follow-up, will automatically reflex Serum Free Light Chains (FLCH). Note: FLCH will remain orderable as a stand-alone test.  2. Random urines will no longer be accepted for Urine Protein Electrophoresis (24hr urine only). MONOCLONAL PROTEIN INVESTIGATION

 3. Free Light Chain Reports will now include the following comment:  “A Free LC Ratio Reference Range of 0.37 to 3.10 is suggested for patients with chronic kidney disease (CKD). The ratio demonstrates a stepwise increase through the CKD stages and remains elevated in patients on hemodialysis.”