Episode 184: Multiple Myeloma Basics

Sub-Interns and future Drs. Di Tran and Jessica Avila explain the symptoms, work up and treatment of multiple myeloma. 

Written by Di Tran, MSIV, Ross University School of Medicine; Xiyuan Yang, MSIV, American University of the Caribbean. Comments by Jessica Avila, MSIV, American University of the Caribbean. Edits by Hector Arreaza, MD.

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Di: Hi everyone, this is Di Tran, 4th year medical student from Ross university.  It’s a pleasure to be back.  To be honest, this project is a part of teamwork of two medical students, myself and another 4th year, her name is XiYuan.  She came from the AUC. Unfortunately, due to personal matters she was unable to make it to the recording today which makes me feel really sad. 

Jessica: My name is Jessica Avila, MSIV, American University of the Caribbean.

Di: The topic we will present today is Multiple Myeloma. Multiple myeloma is typically a rare disease and it’s actually a type of blood cancer that affects plasma cells in the bone marrow.

Jessica: Let’s start with a case: A 66-year-old male comes to his family doctor for an annual health checkup. He is not in any acute distress but he reports that he has been feeling tired and weaker than usual for the last 3 months. He also noticed that he tends to bruise easily. He has a history of arthritis and chronic joint pain, but he thinks his back pain has gotten worse in the last couple of months. Upon checking his lab values, his family doctor found that he has a calcium level of 10.8 and a creatinine level of 1.2, which has increased from his baseline. Given all that information, what do you think his family doctor is suspecting? And what kind of tests she can order for further evaluation?

Di: Those symptoms sound awfully familiar – are we talking about the CRAB? You know, the diagnostic criteria for Multiple Myeloma.

Jessica: Exactly! Those are called “myeloma-defining events.” Do you remember what those are?

Di: CRAB criteria comes in 4 flavors.  It’s HYPERCALCEMIA with >1mg/dL, RENAL INSUFFICIENCY with serum creatinine >2mg/dL, ANEMIA with hemoglobin value <10 g/dL, or more than 2g/dL below normal, and BONE LESION, with one or more osteolytic lesions seen in imaging, be it CT or PET/CT scans.

Jessica: You’re correct about the CRAB criteria! If our patient meets those conditions, myeloma is highly suspected.  Other than the CRAB, there’s something else that has to be met before we can diagnose multiple myeloma.  Patients must undergo a bone marrow biopsy and if there are > 10% plasma cells, PLUS any one or more of the CRAB features, we can make the official diagnosis of multiple myeloma. 

Di:  Before we go deeper, let’s back up a little bit and do a little background.  So, what do we know about the immunoglobulins, also known as antibodies? Back from years of studying from medical school, we know that the plasma cells are the ones that producing the antibodies that help fight infections.  There  are various kinds that come with various functions.  Each antibody is made up of 2 heavy chains and 2 light chains.  For heavy chains, we have A, D, E, G, M and for light chains we have Kappa and Lambda.

Jessica: Usually, the 5 possible types of immunoglobulins for heavy chains would be written as IgG, IgA, IgD, IgE, and IgM.  And the most common type in the bloodstream is nonetheless the IgG. 

Di: What is multiple myeloma? In myeloma, all the abnormal plasma cells make the same type of antibody, the monoclonal antibody.  The cause of myeloma is unknown, but there are lots of studies and evidence that show a number of potential etiologies, including viral, genetic, and exposure to toxic chemicals, especially the Agent Orange, which is a chemical used as herbicide and defoliant. It was used as a chemical warfare by the U.S. military during the Vietnam War from 1961 to 1971.

Jessica: We need to order some specific blood tests to see if there is elevated monoclonal proteins in the blood or urine. So, to begin with we’ll need to take a very thorough history and physical exam. Next, we’ll do labs, such as CBC, basic metabolic panel, calcium, serum beta-2 microglobulin, LDH, total protein, and some not so common tests: serum protein electrophoresis (SPEP), immunofixation of blood or urine (IFE), quantitative immunoglobulins (QIg), serum free light chain assay, and serum heavy/light chain ratio assay.

If any of the results is abnormal, we should consider referring our patient to an oncologist.

Di: Interesting! I read that Multiple Myeloma symptoms vary in different patients.  In fact, about 10-20% of patients with newly diagnosed myeloma do not have any symptoms at all.   Otherwise, classic symptomatic presentations are weakness, fatigue, increased bruising under the skin, reduced urine output, weakened bones that is likely prone to fractures, etc. And if multiple myeloma is highly suspected, a Bone Marrow biopsy should be done with testing for flow cytometry and fluorescent in situ hybridization (FISH). Actually, if any of the “Biomarkers of malignancy (SLIM)” is met we can also diagnose multiple myeloma even without the CRAB criteria. 

Jessica: The diagnosis is made if one or more of the following is found: >= 60% of clonal plasma cells on bone marrow biopsy, > 1 lytic bone lesion on MRI that is at least 5mm in size, or a biopsy confirmed plasmacytoma. 

Di: Imaging comes in at the final step especially if we able to find one or more sites of osteolytic bone destruction > 5mm on an MRI scan.

Jessica: What if the bone marrow biopsy returns > 10% of monoclonal plasma cells, but our patient doesn't have either the CRAB or the Biomarker criteria? 

Di: That’s actually a very good question, since Multiple Myeloma is part of a spectrum of plasma cell disorders. That’s when smoldering myeloma comes into play. It is a precursor of active multiple myeloma. Smoldering myeloma is further categorized as high-risk or low-risk based on specific criteria.

A less severe form is called Monoclonal Gammopathy of Undetermined Significance, or simply MGUS, with < 10% bone marrow involvement. Those are diagnoses we give once we rule out actual multiple myeloma, which are defined by the amount of M-protein in the serum.

Jessica:  When to get started on treatment? Multiple Myeloma is on a spectrum of plasma cells proliferative disorders, starting from MGUS to Smoldering Myeloma, to Multiple Myeloma and to  Plasma Cell Leukemia.  Close supervision/active watching is enough for MGUS and low risk Smoldering Myeloma. But once it has progressed to high-risk smoldering myeloma or to active Multiple Myeloma, chemotherapy is usually required. Some situations may require emergent treatment to improve renal function, reduce hypercalcemia, and to prevent potential infections.

Di: As of 2024, treatment of Multiple Myeloma comprises the Standard-of-Care approved by the FDA. In fact, the quadruple therapy is a combination of 4 different class of drugs that include a monoclonal antibody, a proteasome inhibitor, an immunomodulatory drug, and a steroid. 

Jessica: They are Darzalex (daratumumab), Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone.  Other treatment plans for Multiple Myeloma include chemotherapy, immunotherapy, radiation therapy (for plasmacytomas) and stem cell transplants. The patient will also be on prophylaxis acyclovir and Bactrim while on chemotherapy. Sometimes anticoagulants are also considered because the chemo increases the risk of venous thromboembolic events.

Di: Although the disease is incurable, but with the advancing of novel therapies and clinical trials patients with multiple myeloma are able to live longer.  Problem is the majority of patients diagnosed with Multiple Myeloma are older adults (>65), the risk of falling is adding to multiple complications of the disease itself, such as bone density loss, pain, neurological compromises, distress and weakness.  Palliative care may come in help at any point in time throughout the course of treatment but is most often needed at the very end of the course. Jessica, can you give us a conclusion for this episode?

Jessica: Multiple Myeloma may not be the most common cancer, but we have to be aware of the symptoms and keep it in our differential diagnosis for patients with bone pain, easy bruising, persistent severe headaches, unexplained renal dysfunction, and remember the CRAB: HyperCalcemia, Renal impairment, Anemia and Bone lesions.

Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at [email protected], or visit our website riobravofmrp.org/qweek. See you next week! 

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References:

1. International Myeloma Foundation. (n.d.). International Myeloma Working Group (IMWG) criteria for the diagnosis of multiple myeloma. https://www.myeloma.org/international-myeloma-working-group-imwg-criteria-diagnosis-multiple-myeloma 
2. Laubach, J. P. (2024, August 28). Patient education: Multiple myeloma symptoms, diagnosis, and staging (Beyond the Basics). UpToDate. https://www.uptodate.com/contents/multiple-myeloma-symptoms-diagnosis-and-staging-beyond-the-basics.
3. University of California San Francisco. (n.d.). About multiple myeloma. UCSF Helen Diller Family Comprehensive Cancer Center. https://cancer.ucsf.edu/research/multiple-myeloma/about 
4. Theme song, Works All The Time by Dominik Schwarzer, YouTube ID: CUBDNERZU8HXUHBS, purchased from https://www.premiumbeat.com/.