The Fellow on Call: The Heme/Onc Podcast

Episode 140: Myeloma Series, Pt.1 - Intro to Testing and MGUS

Date: December 3, 2025
Hosts: Ronick, Vivek, Dan
Location: Rouleaux University Medical Center

Episode Overview

The first installment in the updated Myeloma Series tackles the fundamentals of plasma cell dyscrasias, focusing on laboratory testing (SPEP, immunofixation, light chains) and the clinical entity MGUS (Monoclonal Gammopathy of Undetermined Significance). The discussion walks listeners through normal plasma cell biology, the rationale behind workup strategies, and contemporary risk stratification for patients presenting with an abnormal M spike. Mixing clinical anecdotes with up-to-date evidence, the hosts aim to demystify test interpretation and initial management, setting the stage for deeper dives into smoldering myeloma, overt multiple myeloma, and related disorders in subsequent episodes.

Key Discussion Points and Insights

1. Rationale for Revisiting Myeloma Fundamentals

• The landscape of myeloma diagnosis and management has changed considerably in recent years (“…the Myeloma landscape has changed quite a bit.”—Roanoke, 00:21).
• The series revamp ensures both new and returning listeners access the most current practices and evidence.

2. Clinical Context: The Common Plasma Cell Workup

• Case Example: 73-year-old man, normocytic anemia, negative standard workup, eventually found with a SPEP M spike of 1.2—common presentation scenario (Ronick, 04:24).
• Many non-hematologist specialties order SPEP, but interpreting the results is often out of their comfort zone, resulting in frequent hematology referrals (Ronick, 02:41; Dan, 03:42).

3. Normal Plasma Cell Biology Refresher

• Plasma cells are antibody factories—the distinction between immunoglobulin heavy (IgG, IgA, IgM) and light (kappa, lambda) chains is vital for test understanding (Vivek, 05:40).
• The immune system functions optimally with a heterogeneous antibody mix; a shift toward a uniform (clonal) population underpins dyscrasias (Vivek, 07:12).

Notable Quote:

“As the B cell terminally differentiates into this plasma cell to produce antibodies, it chooses either kappa or lambda. ...In a clonal process, you might have an overabundance of one type of the protein.”
– Vivek (07:12)

4. Defining Plasma Cell Dyscrasia

• “Population of plasma cells gone bad”—excessive, clonal production of a single immunoglobulin type (Ronick & Vivek, 08:02–08:11).
• The type and quantity of monoclonal protein drive organ complications (bone lesions, anemia, renal failure, neuropathy) (Vivek, 09:17).

Notable Quote:

“Just to keep things simple…when you have an excess quantity of a specific type of immunoglobulin, there can be downstream consequences.”
– Vivek (09:17)

5. Test Interpretation Deep Dive

• SPEP (Serum Protein Electrophoresis): Separates serum proteins into bands visualized as peaks—the monoclonal (“M”) spike is the hallmark (Dan, 13:38).
• Immunofixation: Determines the heavy and light chain composition of the spike and confirms clonality (Dan, 15:34).
• Serum Free Light Chains: Essential for risk stratification (not just “how much,” but “which type” and “ratio” matter, especially in renal impairment) (Vivek, 18:26).

Notable Quotes:

“SPEP…tells you how much of a protein is present, not which protein is present.”
– Ronick (15:19)

“If you’re sending an SPEP, you should always send serum free light chains…It helps us define how risky this patient…is for having something like multiple myeloma.”
– Vivek (18:26)

6. Urine Protein Studies

• 24-hour urine protein electrophoresis is recommended (not spot urine tests) for detecting monoclonal proteins excreted renally—a “positive UPEP” can raise suspicion for myeloma (Vivek, 20:50).

7. When to Pursue Bone Marrow Biopsy

• Diagnosis of myeloma requires both pathologic (plasma cells >10% or >60%) and clinical criteria—biopsy is the gold standard (Dan, 22:30).
• Not every patient with an M spike needs a biopsy; risk is stratified based on three key features (Vivek, 23:36):
  • Quantity of M spike (>1.5g/dL is higher risk)
  • Type of immunoglobulin (non-IgG is higher risk)
  • Abnormal free light chain ratio

Notable Quote:

“If you have an abnormal free light chain ratio, then even with a lower IgG M spike…we would go ahead and still do that bone marrow biopsy.”
– Vivek (26:49)

8. What is MGUS? (Monoclonal Gammopathy of Undetermined Significance)

• Common and benign in many adults—especially >50 years old (~3% prevalence; up to 6% in African Americans) (Vivek, 23:36).
• Risk of progression to myeloma is about 1% per year, but this risk is not the same for everyone—hence the need for further stratification (Vivek, 23:36).
• Not all MGUS require bone marrow biopsy; low-risk patients are followed with serial labs only (Ronick, 26:09; Vivek, 27:13).

9. Modern Imaging Practices

• PET-CT and MRI have supplanted skeletal surveys for lytic lesion assessment (Dan, 27:58).
• Imaging is triggered if higher-risk features or concerning symptoms are found.

10. Summary Workflow for the Referred Patient

• Initial evaluation should include:
  • SPEP with immunofixation and serum free light chains
  • 24-hour urine protein electrophoresis if indicated
  • Bone marrow biopsy and advanced imaging if high-risk features present

Notable Quote (Workflow Summary):

“Our job is to…make sure that all the different types of testing that's required…is completed…If these things start to show abnormalities…that is where we…do a bone marrow biopsy…and refer for additional radiologic imaging.”
– Ronick (28:45)

Memorable Moments and Quotes

• Pop Culture Humor: Vivek’s enthusiastic plug for “Are You the One?”:

  “It is trashy. It is very trashy…Highly recommend. Are You the One, Vivek?” (01:18)

• Diagnostic Pep Talk:

  “Send more free light chain ratios. That’s what I’ll say.” – Dan (30:27)

Timestamps for Key Segments

• Introductions and Series Overview – 00:04–01:16
• Case Introduction (73-year-old man with anemia) – 04:24
• Back-to-Basics: Plasma Cell and Immunoglobulin Biology – 05:40–09:17
• Clinical Consequences of Monoclonal Protein Production – 09:17–11:42
• Spectrum of Plasma Cell Dyscrasias: MGUS, Smoldering, Myeloma, Waldenstrom’s, Amyloidosis – 11:52–13:38
• SPEP/Immunofixation Explanation – 13:38–16:44
• Serum Free Light Chains & Their Importance – 18:04–19:58
• Urine Protein Electrophoresis Necessity – 20:50–22:30
• Defining Multiple Myeloma & Bone Marrow Biopsy Indications – 22:30–23:36
• MGUS Epidemiology, Risk, & Management – 23:36–27:35
• Modern Imaging Guidelines – 27:35–28:45
• Stepwise Diagnostic Approach Recap – 28:45–29:59
• Wrap-Up and Final Thoughts – 29:59–30:39

Tone and Style

Casual, conversational, and “fellow-to-fellow” practical; the hosts blend evidence-based recommendations with real-world anecdotes, demystifying complex topics in a relatable way. Occasional self-deprecating humor and “pop culture” asides add warmth.

For further reading:

• Rajkumar SV, et al. "Prevalence of MGUS in general and African American populations." NEJM 2006.
• MDCalc MGUS risk stratification calculator (for practical application of discussed criteria).

Next episode:
The team will discuss longitudinal surveillance of MGUS, approach to light chain only MGUS, and introduction to smoldering myeloma.