Multiple Matchaloma

The title is what happens when discussing ideas with one's fiancé while she looks for a good place to get a matcha latte. I will say, catchy. And while matcha is a joke, there is nothing funny about multiple myeloma (MM). My first question is why multiple? Is it just a descriptor? Since there are many smarter folks out there, let me give you what the NIH: National Cancer Institute says about that: "Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors in bone or soft tissue. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma."

Ok, so it is more simple than I imagined but at least I learned something. Don't worry, you can laugh at me if the answer was already obvious to you. Anyway, continuing on, let's start with plasma cells. They begin life as B lymphocytes that form in bone marrow and eventually leave home to start a life of their own in the big city and become rockstars. Or they move to the lymph node, you choose. Once in New York or the lymph nodes, they develop proteins on their surfaces and grow up to be plasma cells. While normally, this process is tightly regulated and wayward (mutated) cells, plasma or otherwise, are taken out before long. In MM, there is a disruption or mutation in the gene that does the regulation allowing misinformed plasma cells to continue multiplying with their current defects, which leads to more defects, and so on and so forth. Kinda like a screwed up, deadly game of telephone where the message gets distorted more and more and more. 

Causes of MM are not specifically known but since it has to do with screwed up genes, you may be able to guess some of the suspected risk factors. Obesity is one, certain occupations (firefighter, industrial worker, etc...) that deal with dangerous chemicals (benzene, toluene, etc...), radiation exposure, and family history. That being said, for the rest of us, avoid those chemicals if you can and try to maintain a normal weight. 

MM starts most often as Monoclonal gammopathy of undetermined significance (MGUS), which from my reading, seems like MM but at a much lower level and often asymptomatic. As such, it is often found on accident and is not often treated. Instead, watching and doing blood tests every 6 months to a year is recommended. Caveat, MGUS can also turn into other issues but I am not going there right now. MGUS may move into the pre-malignant smoldering myeloma, which is not yet full blown overt MM. There are tests and certain levels that are indicative of MGUS, smoldering myeloma, MM respectively. Last point on this issue, MM may also progress to its terminal stage, plasma cell leukemia which is a whole other topic. 

Once someone has MM, there are some non-specific symptoms that may start, anemia, fatigue, weight loss along with more specific ones like bone pain and hypercalcemia due to bone involvement. The International Myeloma Foundation (IMF) has three criteria that are used to narrow down a diagnoses of MM. These are 60% or greater clonal plasma cells on bone marrow examination, "Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved light chain is at least 100mg/L (IDK bro), or multiple focal lesion at least 5mm or larger on MRI. The IMF has other great charts to look at for these diagnostic criteria and their relation to MGUS, smoldering myeloma, and other issues. As the disease progresses bone pain, infection, renal damage, polyuria, polydipsia (from the calcium), fractures, and possible change in mental status may occur. 

Treatment for MM is complex and I will be doing a post about a patient who relapsed after stem cell transplant to get a bit more into that part. There are treatments for MM that are broken down into transplant eligible and ineligible. For those eligible, a 3-4 drug induction treatment is given to reduce the burden of the tumors and kill off (hopefully) many of the mutated plasma cells. The patient will then receive a donation of their own hematopoietic (blood forming) stem cells from healthy bone marrow. That being said, this depends on still having some healthy marrow cells so it probably doesn't work for advanced disease. Once the remaining bone marrow has been cleared out (hopefully) by the induction therapy, the stem cells are given back to replace the malignant marrow cells. This can provide remission for several years but does have risks and is not a sure fire way to achieve remission. However, with modern induction therapy, stem cell transplant, and continuing therapy with newer drugs can help some patients live an extra 10 years. There are also new therapies like CAR-T cell therapy but I won't dive into that pool right now. 

With that, if a patient relapses after transplant, the already horrible disease becomes harder to treat. I’ll be diving in on that later but for now, that’s my story and I’m sticking to it. 

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References

Image of lytic lesions of the skull of an MM patient from Radiopeadia 

Multiple Myeloma from NIH StatPearls

Role of Stem Cell Transplantation in Multiple Myeloma by Devarakonda et al., in Cancers, 2021

Staging System to Predict the Risk of Relapse in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation by Goswami et al., in Frontiers in Oncology 2019

The Diagnosis and Treatment of Multiple Myeloma by Gerecke et al., in 2016 in the journal Deutsches Arzteblatt

The International Myeloma Foundation

The National Cancer Institute