Plasma Cell Dyscrasias

When To Suspect

• Unexplained laboratory abnormalities
  • Anemia
  • Hypercalcemia
  • Elevated “gamma gap” (serum total protein – serum albumin level) > 4
• Bone abnormalities
  • Bone pain with lytic lesions on plain films
  • Age-inappropriate bone fractures with no known risk factors
• Unexplained renal abnormalities
  • Renal failure
  • Proteinuria
• Suspected hyperviscosity syndrome

Initial Workup _(1-4)

• SPEP (Serum Protein Electrophoresis)
  • Detects “M-Protein” spike
• SIFE (Serum Immunofixation Electrophoresis)
  • Identifies heavy chain class
  • Identifies light chain class
  • Does not quantify, therefore, is not a good test to monitor disease
• sFLC (Serum Free Light Chains)
  • Identifies smaller quantities of monoclonal light chains that are NOT bound to heavy chains and classifies them as kappa or lambda (and gives a ratio)
  • May detect paraproteinemia that SIFE cannot, especially in the case of light-chain only dyscrasias
  • Ability to quantify makes it a good method of monitoring disease

• UPEP (Urine Protein Electrophoresis)
• UIFE Urine Immunofixation Electrophoresis)
• 24-Hour UFLC (Urine Free Light Chains)
  • Detects smaller quantities of monoclonal light chains that are NOT bound to heavy chains (Bence-Jones Proteins)
  • Quantifies Bence-Jones proteins

• Bone Marrow Biopsy: Helps differentiate between MGUS and Smoldering Multiple Myeloma

Monoclonal Gammopathy of Undetermined Significance (MGUS)

SPEP: M-Protein spike ❤ g/dL

Bone Marrow Biopsy: <10% Plasma Cells

NO Symptoms

Non-IgM MGUS: May progress to smoldering multiple myeloma or multiple myeloma (risk ~1% per year) ₍₅₎

IgM MGUS: May progress to Waldenstrom Macroglobulinemia, or less frequently, IgM smoldering multiple myeloma or IgM multiple myeloma ₍₆₎

Light Chain MGUS: May progress to light chain multiple myeloma ₍₇₎

Management:

• No treatment necessary
• Monitor with annual labs to CBC, BMP, SPEP, and FLC for progression

Smoldering Multiple Myeloma

SPEP: M-Protein spike >3 g/dL AND/OR Bone Marrow Biopsy: >10% Plasma Cells

NO Symptoms

Management:

• Whole body MRI (or at least spine and pelvic MRI) – if > 1 osteolytic lesion that is > 5 mm on MRI, can classify as Multiple Myeloma ₍₈₎
• High-Risk Smoldering Myeloma (2 of the following 3 features: Bone marrow plasma cells >20 percent, M protein >2 g/dL, FLC ratio >20) ₍₉₎
  • Lenalidomide + Dexamethasone may delay progression to active disease ₍₁₀₎
• Low-Intermediate Risk Smoldering Myeloma
  • Monitoring similar to MGUS, except more frequently, and have to decide risk/benefit of how frequently to repeat imaging

Multiple Myeloma

SPEP: M-Protein spike >3 g/dL

Bone Marrow Biopsy: >10% Plasma Cells

+ Symptoms (“CRAB“: hyperCalcemia, Renal insufficiency, Anemia, Bone pain/lesions). May also manifest as AL Amyloidosis.

Management ₍₁₁₎

• Induction chemotherapy (with VRD – bortezomib, lenalidomide, dexamethasone)
• +/- melphalen-conditioned hematopoeitic stem cell transplant (HCT) if candidate
• Lenalidomide maintenance chemotherapy

References:

1. Rao, M., Lamont, J. L., & Chan, J. (n.d.). Serum Free Light Chain Analysis for the Diagnosis, Management, and Prognosis of Plasma Cell Dyscrasias: Future Research Needs: Identification of Future Research Needs From Comparative Effectiveness Review No. 73. Serum Free Light Chain Analysis for the Diagnosis, Management, and Prognosis of Plasma Cell Dyscrasias: Future Research Needs: Identification of Future Research Needs From Comparative Effectiveness Review No. 73 [Internet]. Retrieved November 12, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK137791/.&nbsp;
2. Leung, N. (n.d.). Chapter 8: Clinical tests for monoclonal proteins. Retrieved November 12, 2021, from https://www.asn-online.org/education/distancelearning/curricula/onco/Chapter8.pdf.&nbsp;
3. Dejoie, T., Attal, M., Moreau, P., Harousseau, J.-L., & Avet-Loiseau, H. (2016, March). Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma. Haematologica. Retrieved November 12, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4815727/.&nbsp;
4. Group, T. I. M. W., Members of the Working Group are listed at the end of the paper.Search for more papers by this author, Alexiou, Kau, Dietzfelbinger, Kremer, Spiess, Schratzenstaller, Arnold, Axelsson, Bachmann, Hällén, Baldini, Guffanti, Cesana, Colombi, Chiorboli, Damilano, Bellaïche, … Wilder. (2003, May 28). Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report of the international myeloma working group. Wiley Online Library. Retrieved November 12, 2021, from https://onlinelibrary.wiley.com/doi/full/10.1046/j.1365-2141.2003.04355.x?sid=nlm%3Apubmed.&nbsp;
5. Kaseb, H., & Hudnall, S. D. (n.d.). MGUS-non IGM. Pathology Outlines – MGUS-non IgM. Retrieved November 13, 2021, from https://www.pathologyoutlines.com/topic/lymphomaMGUS.html.&nbsp;
6. Kaseb, H. (2021, August 22). Monoclonal gammopathy of undetermined significance. StatPearls [Internet]. Retrieved November 13, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK507880/.&nbsp;
7. Cirino, E. (2019, February 15). How serious is MGUS? progression, prognosis, going away on own. Healthline. Retrieved November 13, 2021, from https://www.healthline.com/health/how-serious-is-mgus.&nbsp;
8. Dimopoulos MA;Hillengass J;Usmani S;Zamagni E;Lentzsch S;Davies FE;Raje N;Sezer O;Zweegman S;Shah J;Badros A;Shimizu K;Moreau P;Chim CS;Lahuerta JJ;Hou J;Jurczyszyn A;Goldschmidt H;Sonneveld P;Palumbo A;Ludwig H;Cavo M;Barlogie B;Anderson K;Roodman GD;Raj. (n.d.). Role of magnetic resonance imaging in the management of patients with multiple myeloma: A consensus statement. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Retrieved November 13, 2021, from https://pubmed.ncbi.nlm.nih.gov/25605835/.&nbsp;
9. Lakshman A;Rajkumar SV;Buadi FK;Binder M;Gertz MA;Lacy MQ;Dispenzieri A;Dingli D;Fonder AL;Hayman SR;Hobbs MA;Gonsalves WI;Hwa YL;Kapoor P;Leung N;Go RS;Lin Y;Kourelis TV;Warsame R;Lust JA;Russell SJ;Zeldenrust SR;Kyle RA;Kumar SK; (n.d.). Risk stratification of smoldering multiple myeloma incorporating revised IMWG Diagnostic Criteria. Blood cancer journal. Retrieved November 13, 2021, from https://pubmed.ncbi.nlm.nih.gov/29895887/.
10. Mateos, M.-V., Al., E., Author AffiliationsFrom Hospital Universitario de Salamanca, Others, N. E. L. C. and, Others, V. B. and, Others, N. C. and, S. J. Thomas and Others, Others, Y. G. and, & Monto, A. S. (2013, October 31). Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma: Nejm. New England Journal of Medicine. Retrieved November 13, 2021, from https://www.nejm.org/doi/full/10.1056/nejmoa1300439.&nbsp;
11.  Gaballa MR;Ma J;Tanner MR;Al-Juhaishi T;Bashir Q;Srour SA;Saini NY;Ramdial JL;Nieto Y;Murphy R;Rezvani K;Tang G;Lee HC;Patel KK;Kaufman GP;Manasanch EE;Ullah MR;Kebriaei P;Thomas SK;Weber DM;Orlowski RZ;Shpall EJ;Champlin RE;Qazilbash MH; (n.d.). Real-world long-term outcomes in multiple myeloma with VRD induction, Mel200-Conditioned Auto-HCT, and Lenalidomide Maintenance. Leukemia & lymphoma. Retrieved November 13, 2021, from https://pubmed.ncbi.nlm.nih.gov/34686083/.&nbsp;